CA1341135C - Process and reagent for the determination of the ionic strength or of the specific weight of aqueous liquids - Google Patents
Process and reagent for the determination of the ionic strength or of the specific weight of aqueous liquidsInfo
- Publication number
- CA1341135C CA1341135C CA000604385A CA604385A CA1341135C CA 1341135 C CA1341135 C CA 1341135C CA 000604385 A CA000604385 A CA 000604385A CA 604385 A CA604385 A CA 604385A CA 1341135 C CA1341135 C CA 1341135C
- Authority
- CA
- Canada
- Prior art keywords
- reagent
- buffer substance
- indicator
- aqueous liquid
- specific gravity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
- G01N31/22—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using chemical indicators
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
- G01N33/521—Single-layer analytical elements
Abstract
A process and reagent for the determination of the ionic strength or of the specific gravity of an aqueous liquid by mixing the liquid with a reagent which contains at least one pH buffer substance but no polyelectrolyte polymer or at least one pH buffer substance and/or at least one complex former; and determining the pH value in the liquid and evaluating.
Description
.
a 1341 135 The present invention is concerned with a new process for the determination of the ionic strength or of the specif is gravity of aqueous 1 iquids and with a reagent for carrying out this process.
S Several physical methods are known for the deter-urination of the specifisgravity in urine, for example the determination with hydrometers, urinometers, pykno:neters and refractometers. These methods are admittedly of sufficient exactitude but require a high instrument expense and are time and cost intensive due to the necessary cleaning and calibration of the apparatus.
The measurement of the specific gravity with the help of so called test strips, which can also be evaluated visually, is simpler. Thz test strips have a test field which contains appropriate reagents. The detar:nination can take place in a simple way by dipping t'ne test strip into a urine sample and observing the coloration of the test field. Furthermore, the test strips offer the advantage of being combinable with other urine tests, for example for the detection of glucose, leukocytes, blood and the like, in a multiple test strip with a corresponding number of test fields separate from one another. The measurement of the specific gravity of urine can then take place, with a saving of time, in one step, in addition to the measure-ment of these other parameters. The evaluation can also be carried out with the use of appropriate apparatus.
a 1341 135 The present invention is concerned with a new process for the determination of the ionic strength or of the specif is gravity of aqueous 1 iquids and with a reagent for carrying out this process.
S Several physical methods are known for the deter-urination of the specifisgravity in urine, for example the determination with hydrometers, urinometers, pykno:neters and refractometers. These methods are admittedly of sufficient exactitude but require a high instrument expense and are time and cost intensive due to the necessary cleaning and calibration of the apparatus.
The measurement of the specific gravity with the help of so called test strips, which can also be evaluated visually, is simpler. Thz test strips have a test field which contains appropriate reagents. The detar:nination can take place in a simple way by dipping t'ne test strip into a urine sample and observing the coloration of the test field. Furthermore, the test strips offer the advantage of being combinable with other urine tests, for example for the detection of glucose, leukocytes, blood and the like, in a multiple test strip with a corresponding number of test fields separate from one another. The measurement of the specific gravity of urine can then take place, with a saving of time, in one step, in addition to the measure-ment of these other parameters. The evaluation can also be carried out with the use of appropriate apparatus.
A process for the determination of the specific gravity of urine on a test strip is described in U.S.
Patent Specification No. 4,015,462. A carrier matrix is provided with osmotically breakable microcapsules which contain a liquid; if such a matrix is brought into contact with a sample solution of lower osmolality, then the hydrostatic pressure increases in the microcapsules, the walls of which consist of semi-permeable membrane material. This leads to a rupture of the microcapsules. The rupture of the micro-capsules and the liberation involved therewith of a dye dissolved in the liquid leads to a coloration of the matrix. The intensity of the coloration is proportional to the osmolality or to the specific gravity of the sample solution. A disadvantage of this process is the use of a carrier matrix provided with microcapsules since the production thereof is very difficult because of the necessary exactitude.
A further process for the determination of the specific gravity ~or of the ionic strength on a test strip is described in U.S. Patent Specification No.
Patent Specification No. 4,015,462. A carrier matrix is provided with osmotically breakable microcapsules which contain a liquid; if such a matrix is brought into contact with a sample solution of lower osmolality, then the hydrostatic pressure increases in the microcapsules, the walls of which consist of semi-permeable membrane material. This leads to a rupture of the microcapsules. The rupture of the micro-capsules and the liberation involved therewith of a dye dissolved in the liquid leads to a coloration of the matrix. The intensity of the coloration is proportional to the osmolality or to the specific gravity of the sample solution. A disadvantage of this process is the use of a carrier matrix provided with microcapsules since the production thereof is very difficult because of the necessary exactitude.
A further process for the determination of the specific gravity ~or of the ionic strength on a test strip is described in U.S. Patent Specification No.
4,318,709. The sample is therein mixed with a reagent which contains a weakly acidic or weakly basic poly-electrolyte polymer neutralised to an extent of at least 50~ and an .indicator. The fundamental principle is the proportionality between the specific gravity and the ionic strength of an aqueous solution.
Polyelectrolyte polymers are there designated as being polymers with ionic groups, polyacrylic acid and polyvinylamine being mentioned by way of example.
European Patent Specification No. 0,114,315, published August 1984, describes a reagent which contains a weakly basic polyelectrolyte polymer neutralised by a strong organic acid and an indicator.
European Patent Specification No. 0,114,316, published August 1984, discloses a reagent which contains a weakly acidic polyelectrolyte polymer, in which at least one carboxyl group is present in the form of an ammonium salt, and an indicator.
European Patent Specification No. 0,023,631, published February 1981, discloses a reagent for the determination of the ionic strength or of the specific gravity. Besides a strongly acidic or strongly basic polyelectrolyte polymer, it contains a buffer sub-stance which ensures a pH value of at least 6.5, as well as a pH indicator.
However, processes which are carried out with a reagent which contains polyelectrolyte polymers have the disadvantage that the colour brought about by the pH shift changes in the course of time. The result of this is that the value read off for the specific gravity after 1 minute differs very greatly from the value read off after 2 or even 5 minutes.
Thus, if the test is carried out by persons who have not specially trained for the purpose, such as patients, and the Evaluation is not always undertaken at the same time a;s indicated by the producer of the strip, it can lead to seriously erroneous interpretations of the state of the health of a patent.
Therefore, there is a need for a process for the determination of the ionic strength or of the specific gravity which provides experimental results which remain constant during tha_ test over a comparatively long period of time.
The present. invention seeks to satisfy this need and to provide a process which can also be carried out rapidly and dependably on a test carrier .
Thus, according to the gresent invention, there is provided a process for the determination of the ionic strength or of the specific gravity of an aqueous liquid by mixing the liquid with an appropriate reagent, determining the pH value in the liquid and Evaluating, wherein the reagent contains at least one pH buffer substance but no polyelectrolyte polymer or at least one pH buffer substance and/or at least one complex former.
The present invention also provides a reagent for the determination of the ionic strength or of the specific gravity of an aqueous liquid, wherein it con-tains at least one: pH buffer substance but no poly-electrolyte polymer or at least one pH buffer substance and/or at least one complex former.
The aqueous liquid, the ionic strength of which, also called osmolality, or the specific Gravity. of which can be determined by the process according to the present invention consists essentially of water.
Further components of the liquid can be dissolved and/or non-dissolved components. Dissolved components are ionic and non-ionic: substances. TJndissolved components can be sparingly soluble chemical substances but also other materials, such as biological substances, for example cells.
The liquid can have any desired pH value. Liquids can preferably be investigated with a pH value of 3 to 13 and more preferably of 4 to 9. Liquids with another pH value can also be investigated if the pH value thereof is brought into this range by the addition of an acid or base bef=ore or during the determination.
If the process is used for the determination of the specific gravity it can be used for a range of values of the specific gravity of from 0.95 to 2 and preferably of fro~a 0.99 to 1.2.
Preferred aqueous liquids are salt solutions and body fluids. The process according to the present invention is especially well suited for body fluids, such as perspiration and urine. In particular, it has proved to be useful for urine investigations. In this case, a sample of the urine can be mixed with the reagent _7_ without further preparation steps since not only the specific gravity of the urine with values of 1.00 to 1.04 but also the pH value of the urine with values of 4.5 to 8.0 normally lie in the range preferred for the process according to the present invention.
The reagent with which the liquid is mixed con-tains at least one pH buffer substance and/or at least one complex former. pH buffer substances are well known substances. A pH buffer substance is a mixture of a weak acid with a practically completely dissociated salt of this acid or a mixture of a weak base with a practically completely dissociated salt of this base. This is described, for example, in Rompps Chemie Lexikon, 8th edition, Volume 5, published 1987 by Franckh'sche Verlagshandlung, W. Keller & Co., Stuttgart, Germany, key word "Buffer", which also describes the action of solutions of these buffer substances towards added acids and bases; the pH value of the buffer scarcely changes when acids or bases are added thereto.
According to the present invention, as reagent for the use in the case of the determination of the ionic strength or of the specific gravity especially of urine, pH buffer substances can be used, the pK
value of which in water is from 4 to 12 and preferably from 5.5 to 10. ~~f these, buffer substances with the smallest possible activity coefficient are preferred.
The activity coefficient is especially small in the case of buffer substances which are made up from ions with a -=3.
fv hy:
high effective charge. The activity coefficients of ions and buffer substances in aqueous solutions are known or can be simply determined in known manner (see F. Seel, Grundlagen der analytischen Chemie, pub. Verlag Chemie, Gleinheim, Federal Republic of Germany, brochure "Buffers" of the firm Calbiochem, 1985, pages 12 - 15).
Buffer substances have proved to be especially preferred, the activity coefficient of which at a concentration of 0.1 M is less than 1 and preferably less than 0.9.
Such buffer substances are, in a pH range of from 4 to 11, for example buffers which contain the following ions: phosphate, borate, carbonate, citrate, diethyl-rnalonate or nitrilo-tris-methylene phosphonate. There can also be used zwitterionic buffers, for example glycine buffer or 2-(N-morpholino)-ethanesulphonic acid (MES).
Complex formE:rs in the meaning of the present invention are chemical substances which react with ions with complex forrnat:ion. Especially preferred are complex formers in the complex formation of which with ions at least one proton is liberated.
Such complex formers include, for example, crown ethers, cryptands, podands and multi-nentate ligands which contain weak:Ly acidic or weakly basic groups, for example carboxyl o:r amino groups. Complex formers are preferred which can complex a maximum of one ion per molecule. For the especially exact detection of the ionic strength or of the specific gravity the complex former must be able to form completes with, if possible, all ions present in. the liquid, especially the cations, such as alkali metal and alkaline earth ions, which occur frequently, for example, in urine. Therefore, as complex formers, t:~.e following compounds can, for 'xample, be used:
- crown ethers, cryptands, podands:
18-crown-6-tetracarboxylic acid, id-phenylaza-15-crown-5, hexacyle.ne trisulp'nate, Kryptofix 2221, :Cryptofix :2218 and Kryptofix 211'x, - multi-aentate lig;ands:
ethylenediamine-t:etraacetic acid, nitrilotriacetic acid, diethylenet:riamine-pentaacetic acid, di-(2-aminoethoxy)-ethane-tetraacetic acid, hexamethylene-dinitrilotetraacE:tic acid, nitrilodiacetic acid and N-methylaminodiac:etic acid.
For determinations of the ionic strength or of the specific gravity of liquids which mainly contain dissolved salts which display no substantial buffer capacity, the process is carried out especially preferably with a reagent which consists mainly of one or more complex for~ners. In this case, the reagent must rot necessari:Ly contain pH buffer substances.
If the speci:E'ic gravity of a liquid is to be deter-mined which comprises substances with appreciable -lo-buffer capacity, for example weak bases or acids or salts thereof, then a reagent is preferred which con-tams at least one pH buffer substance. In this case, the contribution of non-ionic compounds, which can also be contained in the .Liquid, to the specific gravity is also taken into account. _Cn addition, the reagent can then also contain one or more complex formers. For the investigation of urine, a reagent composition should be chosen which, dis-solved in an amount of water equivalent to the sample, has a pH value of preferably greater than 5.5.
For reasons of simplicity, it is expedient to keep the number of the components as small as possible.
Therefore, it is also very advantageous to select as buffer substance one which, over and above its pH-r buffering action, also has an ion-complexing action.
Such substances include, for example, nitrilo-tris-(methylenephosphonic acid) and pentasodiurn triphosphate (Na5P3010).
The composition of the reagent, especially with regard to its pH 'value, is preferably so chosen that the pH value after dissolving the reagent in an amount of water equal to the sample is approximately the sane as or greater than and especially preferably is greater than the pH value of the liquid to be investigated. The most appropriate pla value can readily be determined on the basis of a few experiments.
In the case of a reagent applied to an absorbent carrier, this is vE_ry easy to accomplish. The pH value of the impregnation solution is then appropriately adjusted before thE~ impregnation, for example in the case of a reagent :Eor the determination of the specific gravity of urine to a pH value of from 6 to 11 and preferably of from 7 to 9.
The amount o:E pH buffer substances and/or complex formers in the reagent, referred to the amount of liquid to be investigated mixed therewith, is so chosen that the end concentration of these substances of reagent in the sample liquid .amount, in all, to 0.005 to 1.0 mol/
litre and. preferably to 0.005 to 0.2 mol/litre. The form in which the 'reagent is present is not of substantial importance for the determination. For example, the reagent can be used as powder or tablet or in the form of a solution.
In the case of the preferred embodiment of the process on a test strip, the reagent is advantageously applied as a coating to an absorbent carrier, preferred carriers being porous carrier materials or fleece, fleece being understood to be paper-like carriers made up of fibres. Absorbent carriers impregnated with reagent are preferably produced by impregnating the absorbent carrier material with a solution of the reagent and crying, a reagent film thereby being formed on the whole surface and preferably also on the inner surface.
The reagent can also be applied with film-forming and swellable additive materials to a carrier, for example directly on to the test strip. Furthermore, the reagent can contain conventional additive materials, for example stabilisers, wetting agents and/or swelling agents.
The mixing of the liquid with the reagent takes place in a manner which is advantageous for the form chosen for the reagent. If the reagent is applied as coating to an absorbent carrier, then the carrier can simply be brought into contact with the liquid. The liquid is then distributed in the carrier and dissolves off the reagents. This dissolving procedure proceeds especially quickly and completely with the reagent of the process according to the present invention since the reagents are readily soluble lower molecular weight substances.
Due to the action of the reagent on the liquid to be investigated, a pH value is adjusted which is dependent upon the ionic strength or the specific gravity of the liquid to be investigated.
This pH value is determined in the process accord-ing to the present invention. This can take place in known manner, for example also with a pH electrode. The determination with the help of a pH indicator is espec-Tally advantageous since the determination can then also be carried out visually and without additional apparatus.
It is a prerequisite that a pH indicator is used which displays a colour change in a pH range w'nich includes the pH adjusting in the liquid. Such pH
indicators and colour change ranges thereof are known.
For the determination of the ionic strength or of the specific Gravity of urin-~, pH indicators with a pK value of 4 to 12 can be used. Of these, bromothymol blue and thymol blue have proved to be especially suitable.
The pH indicator can be added to the reagent or to the liquid to be investigated even before the mixing or it can be added after the mixing or during the mixing of the reagent with the liquid. The amount of added indicator is such that the colour change can be clearly determined. Preferred concentrations of the indicator in the mixture of reagent and sample liquid are from 0.1 to 100 rnmol/litre and rnore preferably from 1 to 50 mrnol/litre.
Admittedly, in the process according to the present invention, it is possible to carry out the reaction of the reagent with th.e aqueous liquid in a two-phase system, for example in two liquid phases which are not or only slightly miscible with one another, at least a part of the reagent. being present in the non-aqueous phase. I-Iowever, it. is preferable when, during the reaction of the reagent with the liquid or its components, all the reagents and especially the pH buffer substances or complex formers and possibly the pH indicator are dissolved in one phase and preferably in the aqueous phase. In this case, the reaction proceeds especially quickly.
The evaluation in the process according to the S present invention can take place in an especially simple way. For exarnple, by means of a calibration curve, the deter;~ined pl1 value: can be associated wit'n the related ionic strength or t:he specific r~ravity. The calibration curve is obtained by determining the pa values for comparable solutions which have, in each case, different but known ionic strengths or different but known specific weights. In the caS2 Of a visual pH determination with the help of a pH indicator, the resultant colour can, for example, also be compared with colours which have been obtained and recorded for a series of liquids of known ionic strength or specific gravity, for example in a colour scale.
The evaluation can even be undertaken after less than one minute after mixing the reagent and aqueous sample liquid. ThE: process according to the present invention has the advantage that the determined pH value is still constant Even over S minutes after mixing.
This is Especially important when the evaluation requires a comparatively long tune or the evaluation is to be repeated a short time after the first evaluation for reasons of certainty.
An especially preferred embodiment of the process according to t'ne present invention is one for the determination of the specific gravity of urine on a test strip. This test strip has a test field which consists of a fleece which has been impregnated with a solution of the reagent and then dried. The reagent used can be a mixture of a pH buffer substance, for example a phosphate buffer, which when dissolved in water displays a pH value of 8, a complex former, for example nitrilo-triacetic acid, and a pH indicator, for example brorno-thymol blue. The test field is brought into contact with the urine to be investigated, for example by dipping the test strip into the urine and taking it out as soon as the test field is wet. The colour which the test field has then assured is compared with the colour of a standard accompanying the, test strip, each colour of the standard thereby being associated with a specific gravity. The specific gravity to be determined 'nas the value which is associated with the standard with coinciding colour.
The following Examples are given for the purpose of illustrating the: present invention:
Example 1 Production of a te~;t strip for the determination of the ionic stxength or of the specific gravity of salt solutions or urine a) A cellulose fleece (type 23 SL of the fire Schleicher & Schull) was impregnated with an aqueous solution of the following composition:
nitrilo-tris-(methylenephosphonic acid): 120 mM
brornothymol blue: 0.15 % by wt.
The pH value of the solution was adjusted to 8 with a 3.5 i~1 aqueous tetramethylammoniuin hydroxide solution.
The fleece w<3s dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 mm.).
b) A cellulose :Fleece (type 23 SL of the firm Schleicher ~ Schull) was impregnated with an aqueous solution of the following composition:
pentasodium triphasphate (Na5P30~o) 60 mM
bromothymol blue 0.15 % by :at.
The pH value of the solution was adjusted to 8 with 2~I hydrochloric acid.
The fleece was dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 mm.).
c) A cellulose fleece (type 2316 of the firm Binzer) was impregnated with an aqueous solution of the follow-ing composition:
ethylenediamine-tetraacetic acid 0.2 % by wt.
sodium tetraborate 60 mM
thymol blue 0.1 %a by wt.
The pH value: of the solution was adjusted to 10 with a lON aqueous; sodium hydroxide solution.
The fleece was dried and cut up into the size of x 5 mm. and the so produced test field was stuck on to a synthetic re:~i_n strip ( 100 x 5 mm. ) .
d) A cellulose f=leece (type 23 SL of the firm 5 Schleicher & Schull.) was impregnated with an aqueous solution of the following composition:
sodium dihydrogen phosphate 60 mM
2-(N-morpholino)-et:hanesulphonic acid (MES) 40 mM
bis-(aminoethyl)-glycol ether N,N,N' ,i~1'-tetraacetic acid 0.75 % by wt.
brornothymol blue 0.15 % by wt.
The pIi value of the solution was adjusted to 8 with a lON aqueous sodium hydroxide solution.
The fleece was dried and cut up into the size of 5 x 5 mrn. and the so produced test field was stuck on to a synthetic res~~n strip (100 x 5 mm.).
e) A cellulose i_leece (type 2316 of the firm Binzer) was impregnated wit=h an aqueous solution of the follow-ing composition:
sodium dihydrogen phosphate 30 mM
nitrilotriacetic acid 0.2 o by wt.
bromothymol blue 0.1 % by wt.
The pH value of the solution was adjusted to 8 with a lON aqueous sodiuia hydroxide solution:
The fleece w;as dried and cut up into the size of 5 x 5 mm. and the ;so produced test field was stuck on to a synthetic resin strip (100 x 5 mm.).
f) A cellulose fleece (type 23 SL of the firm Schleicher & Schull) was impregnated with an aqueous solution of the following composition:
ethylenediarnine-tetraacetic acid 0.2 %a by wt.
sodium dihydrogen phosphate 30 m~I
bromothymol blue 0.1 % by wt.
The pIi value of the solution was adjusted to 8 with a lON aqueous sodium hydroxide solution.
The fleece was dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 mrn.).
g) A cellulose fleece (type 23 SL of the firm Schleicher S~ Schull) was impregnated with an aqueous solution of the following composition:
diethylmalonic acid 50 mM
nitrilotriacetic acid 0.5 % by wt.
bromothymol blue 0.15 % by wt.
The pH value of the solution was adjusted to 8 with a 3.5i~ tetramethylammonium hydroxide solution.
The fleece wa.s dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 ~~m.).
Example 2 Determination of the specific Qravity of a urine sample A test strip produced according to Example 1 was briefly dipped into urine. After 30 seconds, 1 minute, 2 minutes and 5 ni:inutes, respectively, the colour was 1341 ~ 3 5 compared eaith the colours of a colour scale which had been obtained for urines of known specific gravity.
The values obtained for the specif is gravity at the above-given measurement times were the same. The specific gravity agreed with the specific gravity determined by means of a pyknometer.
Polyelectrolyte polymers are there designated as being polymers with ionic groups, polyacrylic acid and polyvinylamine being mentioned by way of example.
European Patent Specification No. 0,114,315, published August 1984, describes a reagent which contains a weakly basic polyelectrolyte polymer neutralised by a strong organic acid and an indicator.
European Patent Specification No. 0,114,316, published August 1984, discloses a reagent which contains a weakly acidic polyelectrolyte polymer, in which at least one carboxyl group is present in the form of an ammonium salt, and an indicator.
European Patent Specification No. 0,023,631, published February 1981, discloses a reagent for the determination of the ionic strength or of the specific gravity. Besides a strongly acidic or strongly basic polyelectrolyte polymer, it contains a buffer sub-stance which ensures a pH value of at least 6.5, as well as a pH indicator.
However, processes which are carried out with a reagent which contains polyelectrolyte polymers have the disadvantage that the colour brought about by the pH shift changes in the course of time. The result of this is that the value read off for the specific gravity after 1 minute differs very greatly from the value read off after 2 or even 5 minutes.
Thus, if the test is carried out by persons who have not specially trained for the purpose, such as patients, and the Evaluation is not always undertaken at the same time a;s indicated by the producer of the strip, it can lead to seriously erroneous interpretations of the state of the health of a patent.
Therefore, there is a need for a process for the determination of the ionic strength or of the specific gravity which provides experimental results which remain constant during tha_ test over a comparatively long period of time.
The present. invention seeks to satisfy this need and to provide a process which can also be carried out rapidly and dependably on a test carrier .
Thus, according to the gresent invention, there is provided a process for the determination of the ionic strength or of the specific gravity of an aqueous liquid by mixing the liquid with an appropriate reagent, determining the pH value in the liquid and Evaluating, wherein the reagent contains at least one pH buffer substance but no polyelectrolyte polymer or at least one pH buffer substance and/or at least one complex former.
The present invention also provides a reagent for the determination of the ionic strength or of the specific gravity of an aqueous liquid, wherein it con-tains at least one: pH buffer substance but no poly-electrolyte polymer or at least one pH buffer substance and/or at least one complex former.
The aqueous liquid, the ionic strength of which, also called osmolality, or the specific Gravity. of which can be determined by the process according to the present invention consists essentially of water.
Further components of the liquid can be dissolved and/or non-dissolved components. Dissolved components are ionic and non-ionic: substances. TJndissolved components can be sparingly soluble chemical substances but also other materials, such as biological substances, for example cells.
The liquid can have any desired pH value. Liquids can preferably be investigated with a pH value of 3 to 13 and more preferably of 4 to 9. Liquids with another pH value can also be investigated if the pH value thereof is brought into this range by the addition of an acid or base bef=ore or during the determination.
If the process is used for the determination of the specific gravity it can be used for a range of values of the specific gravity of from 0.95 to 2 and preferably of fro~a 0.99 to 1.2.
Preferred aqueous liquids are salt solutions and body fluids. The process according to the present invention is especially well suited for body fluids, such as perspiration and urine. In particular, it has proved to be useful for urine investigations. In this case, a sample of the urine can be mixed with the reagent _7_ without further preparation steps since not only the specific gravity of the urine with values of 1.00 to 1.04 but also the pH value of the urine with values of 4.5 to 8.0 normally lie in the range preferred for the process according to the present invention.
The reagent with which the liquid is mixed con-tains at least one pH buffer substance and/or at least one complex former. pH buffer substances are well known substances. A pH buffer substance is a mixture of a weak acid with a practically completely dissociated salt of this acid or a mixture of a weak base with a practically completely dissociated salt of this base. This is described, for example, in Rompps Chemie Lexikon, 8th edition, Volume 5, published 1987 by Franckh'sche Verlagshandlung, W. Keller & Co., Stuttgart, Germany, key word "Buffer", which also describes the action of solutions of these buffer substances towards added acids and bases; the pH value of the buffer scarcely changes when acids or bases are added thereto.
According to the present invention, as reagent for the use in the case of the determination of the ionic strength or of the specific gravity especially of urine, pH buffer substances can be used, the pK
value of which in water is from 4 to 12 and preferably from 5.5 to 10. ~~f these, buffer substances with the smallest possible activity coefficient are preferred.
The activity coefficient is especially small in the case of buffer substances which are made up from ions with a -=3.
fv hy:
high effective charge. The activity coefficients of ions and buffer substances in aqueous solutions are known or can be simply determined in known manner (see F. Seel, Grundlagen der analytischen Chemie, pub. Verlag Chemie, Gleinheim, Federal Republic of Germany, brochure "Buffers" of the firm Calbiochem, 1985, pages 12 - 15).
Buffer substances have proved to be especially preferred, the activity coefficient of which at a concentration of 0.1 M is less than 1 and preferably less than 0.9.
Such buffer substances are, in a pH range of from 4 to 11, for example buffers which contain the following ions: phosphate, borate, carbonate, citrate, diethyl-rnalonate or nitrilo-tris-methylene phosphonate. There can also be used zwitterionic buffers, for example glycine buffer or 2-(N-morpholino)-ethanesulphonic acid (MES).
Complex formE:rs in the meaning of the present invention are chemical substances which react with ions with complex forrnat:ion. Especially preferred are complex formers in the complex formation of which with ions at least one proton is liberated.
Such complex formers include, for example, crown ethers, cryptands, podands and multi-nentate ligands which contain weak:Ly acidic or weakly basic groups, for example carboxyl o:r amino groups. Complex formers are preferred which can complex a maximum of one ion per molecule. For the especially exact detection of the ionic strength or of the specific gravity the complex former must be able to form completes with, if possible, all ions present in. the liquid, especially the cations, such as alkali metal and alkaline earth ions, which occur frequently, for example, in urine. Therefore, as complex formers, t:~.e following compounds can, for 'xample, be used:
- crown ethers, cryptands, podands:
18-crown-6-tetracarboxylic acid, id-phenylaza-15-crown-5, hexacyle.ne trisulp'nate, Kryptofix 2221, :Cryptofix :2218 and Kryptofix 211'x, - multi-aentate lig;ands:
ethylenediamine-t:etraacetic acid, nitrilotriacetic acid, diethylenet:riamine-pentaacetic acid, di-(2-aminoethoxy)-ethane-tetraacetic acid, hexamethylene-dinitrilotetraacE:tic acid, nitrilodiacetic acid and N-methylaminodiac:etic acid.
For determinations of the ionic strength or of the specific gravity of liquids which mainly contain dissolved salts which display no substantial buffer capacity, the process is carried out especially preferably with a reagent which consists mainly of one or more complex for~ners. In this case, the reagent must rot necessari:Ly contain pH buffer substances.
If the speci:E'ic gravity of a liquid is to be deter-mined which comprises substances with appreciable -lo-buffer capacity, for example weak bases or acids or salts thereof, then a reagent is preferred which con-tams at least one pH buffer substance. In this case, the contribution of non-ionic compounds, which can also be contained in the .Liquid, to the specific gravity is also taken into account. _Cn addition, the reagent can then also contain one or more complex formers. For the investigation of urine, a reagent composition should be chosen which, dis-solved in an amount of water equivalent to the sample, has a pH value of preferably greater than 5.5.
For reasons of simplicity, it is expedient to keep the number of the components as small as possible.
Therefore, it is also very advantageous to select as buffer substance one which, over and above its pH-r buffering action, also has an ion-complexing action.
Such substances include, for example, nitrilo-tris-(methylenephosphonic acid) and pentasodiurn triphosphate (Na5P3010).
The composition of the reagent, especially with regard to its pH 'value, is preferably so chosen that the pH value after dissolving the reagent in an amount of water equal to the sample is approximately the sane as or greater than and especially preferably is greater than the pH value of the liquid to be investigated. The most appropriate pla value can readily be determined on the basis of a few experiments.
In the case of a reagent applied to an absorbent carrier, this is vE_ry easy to accomplish. The pH value of the impregnation solution is then appropriately adjusted before thE~ impregnation, for example in the case of a reagent :Eor the determination of the specific gravity of urine to a pH value of from 6 to 11 and preferably of from 7 to 9.
The amount o:E pH buffer substances and/or complex formers in the reagent, referred to the amount of liquid to be investigated mixed therewith, is so chosen that the end concentration of these substances of reagent in the sample liquid .amount, in all, to 0.005 to 1.0 mol/
litre and. preferably to 0.005 to 0.2 mol/litre. The form in which the 'reagent is present is not of substantial importance for the determination. For example, the reagent can be used as powder or tablet or in the form of a solution.
In the case of the preferred embodiment of the process on a test strip, the reagent is advantageously applied as a coating to an absorbent carrier, preferred carriers being porous carrier materials or fleece, fleece being understood to be paper-like carriers made up of fibres. Absorbent carriers impregnated with reagent are preferably produced by impregnating the absorbent carrier material with a solution of the reagent and crying, a reagent film thereby being formed on the whole surface and preferably also on the inner surface.
The reagent can also be applied with film-forming and swellable additive materials to a carrier, for example directly on to the test strip. Furthermore, the reagent can contain conventional additive materials, for example stabilisers, wetting agents and/or swelling agents.
The mixing of the liquid with the reagent takes place in a manner which is advantageous for the form chosen for the reagent. If the reagent is applied as coating to an absorbent carrier, then the carrier can simply be brought into contact with the liquid. The liquid is then distributed in the carrier and dissolves off the reagents. This dissolving procedure proceeds especially quickly and completely with the reagent of the process according to the present invention since the reagents are readily soluble lower molecular weight substances.
Due to the action of the reagent on the liquid to be investigated, a pH value is adjusted which is dependent upon the ionic strength or the specific gravity of the liquid to be investigated.
This pH value is determined in the process accord-ing to the present invention. This can take place in known manner, for example also with a pH electrode. The determination with the help of a pH indicator is espec-Tally advantageous since the determination can then also be carried out visually and without additional apparatus.
It is a prerequisite that a pH indicator is used which displays a colour change in a pH range w'nich includes the pH adjusting in the liquid. Such pH
indicators and colour change ranges thereof are known.
For the determination of the ionic strength or of the specific Gravity of urin-~, pH indicators with a pK value of 4 to 12 can be used. Of these, bromothymol blue and thymol blue have proved to be especially suitable.
The pH indicator can be added to the reagent or to the liquid to be investigated even before the mixing or it can be added after the mixing or during the mixing of the reagent with the liquid. The amount of added indicator is such that the colour change can be clearly determined. Preferred concentrations of the indicator in the mixture of reagent and sample liquid are from 0.1 to 100 rnmol/litre and rnore preferably from 1 to 50 mrnol/litre.
Admittedly, in the process according to the present invention, it is possible to carry out the reaction of the reagent with th.e aqueous liquid in a two-phase system, for example in two liquid phases which are not or only slightly miscible with one another, at least a part of the reagent. being present in the non-aqueous phase. I-Iowever, it. is preferable when, during the reaction of the reagent with the liquid or its components, all the reagents and especially the pH buffer substances or complex formers and possibly the pH indicator are dissolved in one phase and preferably in the aqueous phase. In this case, the reaction proceeds especially quickly.
The evaluation in the process according to the S present invention can take place in an especially simple way. For exarnple, by means of a calibration curve, the deter;~ined pl1 value: can be associated wit'n the related ionic strength or t:he specific r~ravity. The calibration curve is obtained by determining the pa values for comparable solutions which have, in each case, different but known ionic strengths or different but known specific weights. In the caS2 Of a visual pH determination with the help of a pH indicator, the resultant colour can, for example, also be compared with colours which have been obtained and recorded for a series of liquids of known ionic strength or specific gravity, for example in a colour scale.
The evaluation can even be undertaken after less than one minute after mixing the reagent and aqueous sample liquid. ThE: process according to the present invention has the advantage that the determined pH value is still constant Even over S minutes after mixing.
This is Especially important when the evaluation requires a comparatively long tune or the evaluation is to be repeated a short time after the first evaluation for reasons of certainty.
An especially preferred embodiment of the process according to t'ne present invention is one for the determination of the specific gravity of urine on a test strip. This test strip has a test field which consists of a fleece which has been impregnated with a solution of the reagent and then dried. The reagent used can be a mixture of a pH buffer substance, for example a phosphate buffer, which when dissolved in water displays a pH value of 8, a complex former, for example nitrilo-triacetic acid, and a pH indicator, for example brorno-thymol blue. The test field is brought into contact with the urine to be investigated, for example by dipping the test strip into the urine and taking it out as soon as the test field is wet. The colour which the test field has then assured is compared with the colour of a standard accompanying the, test strip, each colour of the standard thereby being associated with a specific gravity. The specific gravity to be determined 'nas the value which is associated with the standard with coinciding colour.
The following Examples are given for the purpose of illustrating the: present invention:
Example 1 Production of a te~;t strip for the determination of the ionic stxength or of the specific gravity of salt solutions or urine a) A cellulose fleece (type 23 SL of the fire Schleicher & Schull) was impregnated with an aqueous solution of the following composition:
nitrilo-tris-(methylenephosphonic acid): 120 mM
brornothymol blue: 0.15 % by wt.
The pH value of the solution was adjusted to 8 with a 3.5 i~1 aqueous tetramethylammoniuin hydroxide solution.
The fleece w<3s dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 mm.).
b) A cellulose :Fleece (type 23 SL of the firm Schleicher ~ Schull) was impregnated with an aqueous solution of the following composition:
pentasodium triphasphate (Na5P30~o) 60 mM
bromothymol blue 0.15 % by :at.
The pH value of the solution was adjusted to 8 with 2~I hydrochloric acid.
The fleece was dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 mm.).
c) A cellulose fleece (type 2316 of the firm Binzer) was impregnated with an aqueous solution of the follow-ing composition:
ethylenediamine-tetraacetic acid 0.2 % by wt.
sodium tetraborate 60 mM
thymol blue 0.1 %a by wt.
The pH value: of the solution was adjusted to 10 with a lON aqueous; sodium hydroxide solution.
The fleece was dried and cut up into the size of x 5 mm. and the so produced test field was stuck on to a synthetic re:~i_n strip ( 100 x 5 mm. ) .
d) A cellulose f=leece (type 23 SL of the firm 5 Schleicher & Schull.) was impregnated with an aqueous solution of the following composition:
sodium dihydrogen phosphate 60 mM
2-(N-morpholino)-et:hanesulphonic acid (MES) 40 mM
bis-(aminoethyl)-glycol ether N,N,N' ,i~1'-tetraacetic acid 0.75 % by wt.
brornothymol blue 0.15 % by wt.
The pIi value of the solution was adjusted to 8 with a lON aqueous sodium hydroxide solution.
The fleece was dried and cut up into the size of 5 x 5 mrn. and the so produced test field was stuck on to a synthetic res~~n strip (100 x 5 mm.).
e) A cellulose i_leece (type 2316 of the firm Binzer) was impregnated wit=h an aqueous solution of the follow-ing composition:
sodium dihydrogen phosphate 30 mM
nitrilotriacetic acid 0.2 o by wt.
bromothymol blue 0.1 % by wt.
The pH value of the solution was adjusted to 8 with a lON aqueous sodiuia hydroxide solution:
The fleece w;as dried and cut up into the size of 5 x 5 mm. and the ;so produced test field was stuck on to a synthetic resin strip (100 x 5 mm.).
f) A cellulose fleece (type 23 SL of the firm Schleicher & Schull) was impregnated with an aqueous solution of the following composition:
ethylenediarnine-tetraacetic acid 0.2 %a by wt.
sodium dihydrogen phosphate 30 m~I
bromothymol blue 0.1 % by wt.
The pIi value of the solution was adjusted to 8 with a lON aqueous sodium hydroxide solution.
The fleece was dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 mrn.).
g) A cellulose fleece (type 23 SL of the firm Schleicher S~ Schull) was impregnated with an aqueous solution of the following composition:
diethylmalonic acid 50 mM
nitrilotriacetic acid 0.5 % by wt.
bromothymol blue 0.15 % by wt.
The pH value of the solution was adjusted to 8 with a 3.5i~ tetramethylammonium hydroxide solution.
The fleece wa.s dried and cut up into the size of 5 x 5 mm. and the so produced test field was stuck on to a synthetic resin strip (100 x 5 ~~m.).
Example 2 Determination of the specific Qravity of a urine sample A test strip produced according to Example 1 was briefly dipped into urine. After 30 seconds, 1 minute, 2 minutes and 5 ni:inutes, respectively, the colour was 1341 ~ 3 5 compared eaith the colours of a colour scale which had been obtained for urines of known specific gravity.
The values obtained for the specif is gravity at the above-given measurement times were the same. The specific gravity agreed with the specific gravity determined by means of a pyknometer.
Claims (47)
1. A process for the determination, at a pH of 3 to 13, of the ionic strength or of the specific gravity, in the range of from 0.95 to 2, of an aqueous liquid comprising:
mixing the liquid with a reagent to form a mixture of the liquid and the reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre, said reagent comprising a pH indicator and one component selected from i), ii) and iii):
i) at least one pH buffer substance, said buffer substance and said reagent being free of polyelectrolyte polymer;
ii) at least one pH buffer substance and at least one complex former, iii) at least one complex former;
determining the pH value in the mixture, and evaluating the determined pH as a measure of the ionic strength or specific gravity.
mixing the liquid with a reagent to form a mixture of the liquid and the reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre, said reagent comprising a pH indicator and one component selected from i), ii) and iii):
i) at least one pH buffer substance, said buffer substance and said reagent being free of polyelectrolyte polymer;
ii) at least one pH buffer substance and at least one complex former, iii) at least one complex former;
determining the pH value in the mixture, and evaluating the determined pH as a measure of the ionic strength or specific gravity.
2. A process according to claim 1, in which said reagent comprises at least one pH buffer substance and is free of polyelectrolyte polymer.
3. A process according to claim 1, in which said reagent comprises a pH buffer substance and a complex former.
4. A process according to claim 1, in which said reagent consists essentially of said pH indicator and at least one complex former.
5. A process according to claim 1, wherein the reagent is impregnated on to an absorbent carrier prior to said mixing.
6. A process according to claim 1, wherein said at least one pH buffer substance in i) and ii) has an activity coefficient of less than 1 at a concentration of 0.1M.
7. A reagent for the determination, at a pH of 3 to 13, of the ionic strength or of the specific gravity, in the range of from 0.95 to 2, of an aqueous liquid, comprising a pH indicator and one component selected from i), ii) and iii):
i) at least one pH buffer substance, said buffer substance and reagent being free of polyelectrolyte polymer;
ii) at least one pH buffer substance and at least one complex former;
iii) a complex former.
i) at least one pH buffer substance, said buffer substance and reagent being free of polyelectrolyte polymer;
ii) at least one pH buffer substance and at least one complex former;
iii) a complex former.
8. A reagent according to claim 7, which comprises the at least one pH buffer substance and is free of polyelectrolyte polymer.
9. A reagent according to claim 7, which comprises a pH buffer substance and a complex former.
10. A reagent according to claim 7, which comprises the complex former.
11. A reagent according to claim 7, 8, 9 or 10, impregnated on to an absorbent carrier.
12. A reagent according to claim 7, wherein, said at least one pH buffer substance in i) and ii) has an activity coefficient of less than 1 at a concentration of 0.1M.
13. A reagent according to claim 8, wherein said at least one pH buffer substance has an activity coefficient of less than 1 at a concentration of 0.1M.
14. A reagent according to claim 9, wherein said pH
buffer substance has an activity coefficient of less than 1 at a concentration of 0.1M.
buffer substance has an activity coefficient of less than 1 at a concentration of 0.1M.
15. A test strip for the determination of the ionic strength or of the specific gravity of an aqueous liquid, comprising a support and an absorbent carrier impregnated with a reagent fixed thereon, wherein the reagent: is as defined in claim 7, 8, 9, 10, 11, 12 or 13.
16. A reagent according to claim 8, in which the at least one pH buffer substance has a pK value in water of from 5.5 to 10 and an activity coefficient of less than 0.9 at a concentration of 0.1M.
17. Use of a pH indicator and a pH buffer free of polyelectrolyte polymer for the determination at a pH
of 3 to 13 of the ionic strength or of the specific gravity of an aqueous liquid in the range of from 0.95 to 2.
of 3 to 13 of the ionic strength or of the specific gravity of an aqueous liquid in the range of from 0.95 to 2.
18. Use of a pH indicator and a pH buffer together with a complex former for the determination at a pH of 3 to 13 of the ionic strength or of the specific gravity of an aqueous liquid in the range of from 0.95 to 2.
19. Use of a pH indicator and a complex former for the determination at a pH of 3 to 13 of the ionic strength or of the specific gravity of an aqueous liquid in the range of from 0.95 to 2.
20. A process for the determination, at a pH of 3 to 13, of the ionic strength of an aqueous liquid comprising:
mixing the liquid with a reagent to form a mixture of the liquid and the reagent having a concentration of: said reagent of 0.005 to 1.0 mol/litre, said reagent, comprising a pH indicator and one component selected from i), ii) and iii):
i) at least on.e pH buffer substance, said buffer substance and reagent being free of polyelectrolyte polymer;
ii) a pH buffer substance and a complex former;
iii) a complex former;
determining the pH value, and evaluating the determined pH as a measure of the ionic strength.
mixing the liquid with a reagent to form a mixture of the liquid and the reagent having a concentration of: said reagent of 0.005 to 1.0 mol/litre, said reagent, comprising a pH indicator and one component selected from i), ii) and iii):
i) at least on.e pH buffer substance, said buffer substance and reagent being free of polyelectrolyte polymer;
ii) a pH buffer substance and a complex former;
iii) a complex former;
determining the pH value, and evaluating the determined pH as a measure of the ionic strength.
21. A reagent for determining, at a pH of 3 to 13, the ionic strength or specific gravity, in the range of from 0.95 to 2, of an aqueous liquid containing a plurality of different rations comprising:
i) at least one water soluble pH buffer, ii) at least one water soluble complex former which can complex with more than one different ration present in said aqueous liquid and which releases at least one proton upon complex formation with a ration, and iii) a water soluble pH indicator.
i) at least one water soluble pH buffer, ii) at least one water soluble complex former which can complex with more than one different ration present in said aqueous liquid and which releases at least one proton upon complex formation with a ration, and iii) a water soluble pH indicator.
22. The reagent of claim 21, wherein said at least one pH buffer has an activity coefficient of less than 1 at a concentration of 0.1M.
23. The reagent of claim 21 or 22, wherein said at least one complex former is a crown ether, a cryptand, a podand or a multi-dentate ligand.
24. The reagent of claim 21 or 22, wherein said at least one water soluble complex former is bis-(aminoethyl)-glycol-ether-N,N,N',N'-tetraacetic acid.
25. The reagent of claim 24, wherein said at least one water soluble pH buffer is a sodium phosphate at a pH of from 4 to 11.
26. The reagent of claim 24, wherein said at least one water soluble pH indicator is bromothymol blue.
27. The reagent, of claim 21 ar 22, wherein said at least one pH buffer comprises 2-(N-morpholino)-ethanesulfonic acid, said at least one complex former is bis-(aminoethyl)-glycol-ether-N,N,N',N'-tetraacetic acid, and said pH indicator is bromothymol blue.
28. A process for determining, at a pH of 3 to 13, ionic strength or specific gravity, in the range of from 0.95 to 2, of an aqueous liquid, comprising:
contacting said liquid with a non-polyelectrolyte polymer-containing reagent comprising:
i) a pH buffer substance, and ii) a pH indicator, to form an aqueous solution of said aqueous liquid and reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre; and measuring pH of said solution after said contacting as a measure of ionic, strength or specific gravity of said aqueous liquid.
contacting said liquid with a non-polyelectrolyte polymer-containing reagent comprising:
i) a pH buffer substance, and ii) a pH indicator, to form an aqueous solution of said aqueous liquid and reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre; and measuring pH of said solution after said contacting as a measure of ionic, strength or specific gravity of said aqueous liquid.
29. A process of claim 28, wherein said pH buffer substance has an activity coefficient of less than 1 at a concentration of 0.1M.
30. A process of claim 28, wherein said pH buffer substance contains at least one ion selected from the group consisting of phosphate, borate, carbonate, citrate, diethylmalonate and nitrilo-tris-methylene phosphonate.
31. A process of claim 28, 29 or 30, wherein said pH
buffer substance has a pK value of from 4 to 12.
buffer substance has a pK value of from 4 to 12.
32. A process of claim 31, wherein said pH buffer substance has a pK value of from 5.5 to 10.
33. A process of claim 28, 29, 30, 31 or 32, wherein said pH buffer substance is zwitterionic.
34. A process of claim 33, wherein said pH buffer substance contains glycine or 2-(N-morpholino)-ethane sulphonic acid.
35. A process for determining, at a pH of 3 to 13, ionic strength or specific gravity, in the range of from 0.95 to 2, of an aqueous liquid comprising:
contacting said liquid with a reagent consisting essentially of:
i) a cation complex former which releases a proton upon complexation of a cation therewith, and ii) a pH indicator, to form an aqueous solution of said aqueous liquid and said reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre, under conditions favoring complexing of rations in said aqueous liquid to said complex former with release of protons therefrom, and measuring the pH of said solution as a measure of ionic strength or specific gravity of said aqueous liquid.
contacting said liquid with a reagent consisting essentially of:
i) a cation complex former which releases a proton upon complexation of a cation therewith, and ii) a pH indicator, to form an aqueous solution of said aqueous liquid and said reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre, under conditions favoring complexing of rations in said aqueous liquid to said complex former with release of protons therefrom, and measuring the pH of said solution as a measure of ionic strength or specific gravity of said aqueous liquid.
36. A process of claim 35, wherein said reagent is impregnated on an absorbent carrier, prior to said contacting.
37. A process of claim 35 or 36, wherein said liquid is urine.
38. A process of claim 35, 36 or 37, wherein said complex former is a crown ether, a cryptand, a podand or a multi-dentate ligand.
39. A process of claim 35, wherein said reagent is used at a concentration of from 0.005 to 0.2 mole/liter of liquid.
40. A process of claim 35, wherein said reagent is a powder tablet or solution.
41. A process of claim 35, 36, 37, 38, 39 or 40, wherein said pH indicator displays a color change when said complex former complexes to said cations.
42. A process of claim 35, 36, 37, 38, 39, 40 or 41, wherein said pH indicator is bromothymol blue or thymol blue.
43. A process of claim 35, 36, 37, 38, 39, 40, 41 or 42, wherein said pH indicator is added at a concentration of from 0.1 to 100 mmol/liter.
44. A process of claim 35, wherein said pH indicator is added at a concentration of from 1 to 50 mmol/liter.
45. A process of claim 35, 36, 37, 38, 39, 40, 41, 42, 43 or 44, comprising measuring the pH within one minute after adding said reagent.
46. A process of claim 35, wherein said reagent is in the form of a solution.
47. A process for determining, at a pH of 3 to 13, ionic strength or specific gravity, in the range of from 0.95 to 2, of an aqueous liquid, comprising:
contacting said aqueous liquid with a solution containing a reagent consisting essentially of:
(i)a pH buffer. substance, and (ii)a cation complex former which releases at least one proton upon complexation of a cation therewith.
to form an aqueous solution of said aqueous liquid and reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre, and measuring pH of said solution as a measure of ionic strength or specific gravity of said aqueous liquid.
contacting said aqueous liquid with a solution containing a reagent consisting essentially of:
(i)a pH buffer. substance, and (ii)a cation complex former which releases at least one proton upon complexation of a cation therewith.
to form an aqueous solution of said aqueous liquid and reagent having a concentration of said reagent of 0.005 to 1.0 mol/litre, and measuring pH of said solution as a measure of ionic strength or specific gravity of said aqueous liquid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3823151.4 | 1988-07-08 | ||
| DE3823151A DE3823151C2 (en) | 1988-07-08 | 1988-07-08 | Method for determining the ionic strength or specific gravity of aqueous liquids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1341135C true CA1341135C (en) | 2000-11-07 |
Family
ID=6358243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000604385A Expired - Fee Related CA1341135C (en) | 1988-07-08 | 1989-06-29 | Process and reagent for the determination of the ionic strength or of the specific weight of aqueous liquids |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US5064615A (en) |
| EP (1) | EP0349934B1 (en) |
| JP (1) | JPH0718865B2 (en) |
| KR (1) | KR920000055B1 (en) |
| CN (1) | CN1017937B (en) |
| AT (1) | ATE154439T1 (en) |
| AU (2) | AU606290B2 (en) |
| CA (1) | CA1341135C (en) |
| DD (1) | DD284087A5 (en) |
| DE (2) | DE3823151C2 (en) |
| ES (1) | ES2104557T3 (en) |
| GR (1) | GR3024184T3 (en) |
| LV (1) | LV10810B (en) |
| RU (1) | RU1809922C (en) |
| UA (1) | UA18255A (en) |
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| DE4116108A1 (en) * | 1991-05-17 | 1992-11-19 | Behringwerke Ag | REAGENT FOR DETERMINING ION STRENGTH AND OF THE SPECIFIC WEIGHT OF AQUEOUS LIQUIDS AND METHOD |
| US5565363A (en) * | 1991-10-21 | 1996-10-15 | Wako Pure Chemical Industries, Ltd. | Reagent composition for measuring ionic strength or specific gravity of aqueous solution samples |
| US5267532A (en) * | 1992-05-05 | 1993-12-07 | Anitox Corporation | pH-indicating material and cat litter containing same |
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| US5302531A (en) * | 1992-10-22 | 1994-04-12 | Miles Inc. | Composition for the semiquantitative determination of specific gravity of a test sample |
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| US8742198B2 (en) * | 2010-12-01 | 2014-06-03 | Kimberly-Clark Worldwide, Inc. | Dehydration sensors having polymeric base-buffered inks |
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| DE2510633C3 (en) * | 1975-03-12 | 1978-07-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Diagnostic agent for the detection of protein in body fluids and indicator dyes suitable therefor |
| US4015462A (en) * | 1976-01-08 | 1977-04-05 | Miles Laboratories, Inc. | Device and method for the determination of the specific gravity or osmolality of a liquid |
| US4108727A (en) * | 1976-08-23 | 1978-08-22 | Miles Laboratories, Inc. | Method, composition and device for determining the specific gravity or osmolality of a liquid |
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-
1988
- 1988-07-08 DE DE3823151A patent/DE3823151C2/en not_active Expired - Fee Related
-
1989
- 1989-06-26 US US07/371,208 patent/US5064615A/en not_active Expired - Lifetime
- 1989-06-29 CA CA000604385A patent/CA1341135C/en not_active Expired - Fee Related
- 1989-07-01 ES ES89112032T patent/ES2104557T3/en not_active Expired - Lifetime
- 1989-07-01 EP EP89112032A patent/EP0349934B1/en not_active Expired - Lifetime
- 1989-07-01 AT AT89112032T patent/ATE154439T1/en not_active IP Right Cessation
- 1989-07-01 DE DE58909802T patent/DE58909802D1/en not_active Expired - Lifetime
- 1989-07-04 AU AU37850/89A patent/AU606290B2/en not_active Expired
- 1989-07-05 UA UA4614517A patent/UA18255A/en unknown
- 1989-07-05 DD DD89330465A patent/DD284087A5/en not_active IP Right Cessation
- 1989-07-05 RU SU894614517A patent/RU1809922C/en active
- 1989-07-07 JP JP1174300A patent/JPH0718865B2/en not_active Expired - Lifetime
- 1989-07-08 CN CN89104644A patent/CN1017937B/en not_active Expired
- 1989-07-08 KR KR1019890009724A patent/KR920000055B1/en not_active IP Right Cessation
-
1990
- 1990-11-19 US US07/615,372 patent/US5106752A/en not_active Expired - Lifetime
- 1990-12-17 AU AU68121/90A patent/AU615853B2/en not_active Expired
-
1993
- 1993-06-02 LV LVP-93-469A patent/LV10810B/en unknown
-
1997
- 1997-07-22 GR GR970401829T patent/GR3024184T3/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2104557T3 (en) | 1997-10-16 |
| DE3823151A1 (en) | 1990-01-11 |
| EP0349934A3 (en) | 1990-10-31 |
| CN1017937B (en) | 1992-08-19 |
| US5106752A (en) | 1992-04-21 |
| GR3024184T3 (en) | 1997-10-31 |
| DE3823151C2 (en) | 1997-07-10 |
| LV10810B (en) | 1995-12-20 |
| AU6812190A (en) | 1991-04-11 |
| EP0349934B1 (en) | 1997-06-11 |
| AU3785089A (en) | 1990-02-15 |
| EP0349934A2 (en) | 1990-01-10 |
| AU606290B2 (en) | 1991-01-31 |
| LV10810A (en) | 1995-08-20 |
| KR920000055B1 (en) | 1992-01-06 |
| ATE154439T1 (en) | 1997-06-15 |
| US5064615A (en) | 1991-11-12 |
| JPH0266451A (en) | 1990-03-06 |
| AU615853B2 (en) | 1991-10-10 |
| DE58909802D1 (en) | 1997-07-17 |
| KR900002072A (en) | 1990-02-28 |
| UA18255A (en) | 1997-12-25 |
| DD284087A5 (en) | 1990-10-31 |
| JPH0718865B2 (en) | 1995-03-06 |
| CN1039656A (en) | 1990-02-14 |
| RU1809922C (en) | 1993-04-15 |
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