Explore our in-depth article on accurately determining the water content of APIs and medicinal products by according to accepted methods from IP, BP, USP, and Ph. Eur.

Water Content (Moisture Content) Test Procedure

1.0     Objective

• • The objective of this General Test Procedure (GTP) is to describe the procedure to be used for performing of water content.

2.0     Principle/Reaction

• • The titrimetric determination of water content is based upon the quantitative reaction of water with an anhydrous solution of sulfur dioxide and iodine in the presence of a buffer that reacts with hydrogen ions.

• • In the original titrimetric solution, known as Karl Fischer Reagent, the sulfur dioxide and iodine are dissolved in pyridine and methanol.

• • The test specimen may be titrated with the reagent directly, or the analysis may be carried out by a residual titration procedure.

• • The stoichiometry of the reaction is not exact, and the reproducibility of a determination depends upon such factors as the relative concentrations of the reagent ingredients, the nature of the inert solvent used to dissolve the test specimen, and the technique used in the particular determination.

• • Therefore, an empirically standardized technique is used in order to achieve the desired accuracy.

• • Precision in the water content method is governed largely by the extent to which atmospheric moisture content is excluded from the system.

• • The titration of water is usually carried out with the use of anhydrous methanol as the solvent for the test specimen;

• • however, other suitable solvents may be used for special or unusual test specimens as mentioned.

• • Water content determination by gravimetric method is based on the principle, that is loss in weight of sample in % w/w, when drying at 105º C for given time period.

3.0     Requirements for Water Content Determination:

• Water Content Determination as per IP

• • Apparatus as per method

• • KF Reagent

• • Dried Methanol

• • Disodium Tartrate

• • Purified water

• Water Content Determination as per USP

• • Same as per IP

• Water Content Determination as per BP/ph.Eur.

• • Same as per IP

4.0     Procedure for Water Content / Moisture Content determination:

• Water Content Determination as per Indian Pharmacopoeia (IP)

• • Titrimetric method. Use method 1 unless otherwise directed.

• • Primary Standardization of the reagent disodium Tartrate:

  • Place about 50 ml of dehydrated methanol in the titration vessel and add sufficient Karl Fischer reagent to give the characteristics end-point.

• • Add quickly 150 to 350 mg of disodium tartrate, C₄H₄O₆Na₂, 2H₂O in appropriate form accurately weighed by difference and titrate to the endpoint.

• • The water equivalence factor, F, in mg of water per ml of the reagent is given by the expression 0.1566 w/v, where “w” is the weight, in mg of the disodium tartrate or water and “v” is the volume in ml of the reagent required.

• • Secondary standardization of the reagent:

• • The Karl Fischer reagent may alternatively be standardized for each day’s use against a water methanol solution standardized as follows.

• • Add 2.0 ml of water to 1000.0 ml of dehydrated methanol.

• • Retain a portion of the methanol used for a blank determination.

• • Place 25 ml, accurately measured of the water methanol solution in the titration vessel and titrate with Karl Fischer reagent.

• • Perform a blank titration on 25 ml accurately measured, of the methanol used and make any necessary correction.

• • The water content in mg per ml of the water methanol solution is given by the expression VF/25 in which V is the volume, in ml, of Karl Fischer reagent required and F is the water equivalent factor of the reagent determined against sodium tartrate as directed under Primary standardization of the reagent.

• • Primary standardization of the reagent by water:

  • For the precise determination of significant amounts of water (1 % or more), use purified water as the reference substance.

• • Quickly add about 25 mg of water, accurately weighed by difference, from a weighing pipet or from a pre-calibrated syringe or micropipette or any other suitable procedure.

• • Titrate to the endpoint.

• • Calculate the water equivalence factor, F, in mg of water per ml of reagent, by the formula;

W/V,

In which W is the weight, in mg, of the water, and V is the volume, in ml of the reagent required.

Note: Secondary standardization is not required if primary standardization is done by water.

• • Apparatus for Water Content Determination:

  • A titration vessel of about 60 ml capacity is fitted with two platinum electrodes, about 0.05 sq. cm in area and about 2.5 cm apart a nitrogen inlet tube, a stopper which accommodates the burette tip and a vent tube protected by a suitable desiccant such as phosphorous pentoxide or silica gel.

• • The substance being examined is introduced through an inlet or side arm which can be closed by a ground stopper.

• • Stirring is done magnetically or by means of a steam of dried nitrogen passed through the solution during the titration. The air in the entire system should be kept dry during the titration.

• • The end-point is determined by amperometry.

• • The circuit consists of a potentiometer of about 2000 ohms connected across a 1.5 v battery.

• • The resistance is adjusted so that an initial low current passes through the electrodes.

• • On adding the reagent the needle of the microammeter shows a deflection but returns immediately to its starting position.

• • At the end point of the titration a slight excess of the reagent produces a deflection the persists for not less than half a minute.

• • Method A for Water Content Determination:

  • Unless otherwise directed add about 50 ml of dehydrated methanol to the titration vessel and titrate to the electrometric end point with the Karl Fischer reagent.

• • Transfer quickly the prescribed amount of the substance being examined, accurately weighed to the titration vessel.

• • Stir for 1 minute and titrate again to the electrometric end point using the Karl Fischer Reagent.

• • The water content of the sample, in mg is given by the expression S × F, in which S is the volume, in ml of the Karl Fischer reagent used to titrate the sample and F is the water equivalent factor.

• • % of water may be calculated by following formula.

% water = Burette reading ×KF Factor (mg/ml) × 100

Sample weight in mg

• • Method B for Water Content Determination :

  • This method should be followed for samples that react with difficulty or too slowly for convenient direct titration with the Karl Fischer reagent.

• • Unless otherwise directed add about 10 ml of dehydrated methanol to the titration vessel and titrate to the electrometric end point with the Karl Fischer reagent.

• • Transfer quickly the prescribed amount accurately weighed, of the substance being examined to the titration vessel followed by an accurately measured amount of Karl Fischer reagent sufficient to given an excess of about 1 ml.

• • Allow to stand, protected from light, for 1 minute, stirring well.

• • Titrate the excess of the reagent to the electrometric endpoint with dehydrated methanol to which has been added an accurately known amount of water equivalent to about 0.25 % w/v.

• • Azeotropic Distillation Method Apparatus;

 

• • The apparatus (see fig.) consists of a round- bottomed, 500 ml flask (A) connected by means of a trap (B). 23.5 to 24.0 cm long, to a vertical reflux condenser of the straight-tube type (C), by ground glass joints.

• • The condenser is approximately 40 cm long and has a bore diameter of not less than 8 mm. The connecting tube (D) is 9 to 11 mm in internal diameter.

• • The receiving tube (E) has a 5ml capacity and its cylindrical part, 14.6 to 15.6 cm in length is graduated in 0.1 ml sub divisions.

• • The flask is heated in an oil-bath or in an electric mantle.

• • The upper portion of the flask and the connecting tube may be insulated.

• • Before use, the condenser and receiving tube should be cleaned with chromic acid mixture, thoroughly rinsed with water and dried in an oven.

• • Method C for Water Content Determination:

  • Weigh accurately a quantity of the substance being examined that is expected to yield 2 to 4 ml of water and transfer to the dry flask.

• • If the substance is semisolid, weigh it in a metal foil, fold the foil carefully and pass through it the neck of the flask.

• • To prevent bumping add enough washed and dried sand to cover the bottom of the flask or a few capillary melting-point tubes, 10cm long, sealed at the upper end.

• • Add about 200 ml of prepared toluene, connect the apparatus and fill the receiving tube (E) with prepared toluene poured through the top of the condenser.

• • Heat the flask gently for 15 minutes and when the toluene begins to boil, distilled at the rate of about 2 drops per second until most of the water has distilled over, then increase the rate to about 4 drops per second.

• • When the water has apparently completely distilled over, rinse the inside of the cylinders tube with prepared toluene with the aid of a tube brush attached to a copper wire and saturated with prepared toluene.

• • Continue distillation for 5 minutes, remove the heat and allow the receiving tube to cool to room temperature.

• • If any droplets of water stick to the walls of the receiving tube, scrub them using a copper wire with a rubber band wrapped around it and washed with prepared toluene. After complete separation of water and toluene in the tube, read off the volume of water in the tube and calculate the content of water as a percentage w/w, assuming the weight per ml of water to be 1.0.

• Water Content Determination as per United States Pharmacopoeia (USP)

• • Method I (Titrimetric) – Water Content Determination

• • Determine the water by method Ia, unless otherwise specified in the individual monograph.

• • Method Ia (Direct Titration for Water Content)

• • Any apparatus may be used that provides for adequate exclusion of atmospheric moisture and determination of the endpoint.

• • In the case of a colorless solution that is titrated directly, the endpoint may be observed visually as a change in colour from canary yellow to amber.

• • The reverse is observed in the case of a test specimen that is titrated residually.

• • More commonly, however the endpoint is determined electrometrically with an apparatus employing an electrical circuit a pair of platinum electrodes immersed in the solution to be titrated.

• • At the endpoint of the titration a slight excess of the reagent increases the flow of current which is detected by the electrodes for not less than 30s.

• • The time is shortest for substances that dissolve in the reagent. With some automatic titrator, the abrupt change in current or potential at the end point serves to close a solenoid operated valve that controls the burets delivering the titrant.

• • Commercially available apparatus generally comprises a closed system consisting of one or two automatic burets and a tightly covered titration vessel fitted with the necessary electrodes and a magnetic stirrer.

• • The air in the system is kept dry with a suitable desiccant, and the titration vessel may be purged by means of a stream of dry nitrogen or current of dry air.

• Karl Fisher Reagent Preparation

  • Prepare the Karl Fischer reagent as follows.

• • Add 125 g of iodine to a solution containing 670 ml of methanol and 170 ml of pyridine, and cool.

• • Place 100 ml of pyridine in a 250 ml graduated cylinder, and keeping the pyridine cold in an ice bath. Pass in dry sulfur dioxide until the volume reaches 200 ml.

• • slowly add this solution with shaking, to the cooled iodine mixture. Shake to dissolve the iodine, transfer the solution to the apparatus, and allow the solution to stand overnight before standardizing.

• • One ml of this solution when freshly prepared is equivalent to approximately 5 mg of water, but it deteriorates gradually, therefore, standardize it within 1 hour before use, or daily if in continuous use.

• • Protect from light while in use.

• • Store any bulk stock of the reagent in a suitable sealed, glass stoppered container, fully protected from light, and under refrigeration.

• • A commercially available, stabilized solution of Karl Fischer type reagent may be used.

• • Commercially available reagents containing solvents or bases other than pyridine or alcohols other than methanol may be used also.

• • These may be single solutions or reagents formed in situ by combining the components of the reagents present in two discrete solutions.

• • The diluted reagent called for in some STPs should be diluted as directed by the manufacturer.

• • Either methanol or other suitable solvent, such as ethylene glycol mono methyl ether may be sued as the diluent.

• • Test preparation for Water Content :

• • Unless otherwise specified in the individual STP, use an accurately weighed or measured amount of the specimen under test estimated to contain 10 to 250mg of water.

• • Where the specimen under test is an aerosol with propellant, store it in a freezer for not less than 2 hours, open the container and test 10.0 ml of the well mixed specimen.

• • In titrating the specimen determine the endpoint at a temperature of 10º or higher.

• • Where the specimen under test is a capsule, use a portion of the mixed contents of not fewer than 4 capsules.

• • Where the specimen under test is a tablet, use powder form not fewer than 4 tablets ground to a fine powder in an atmosphere of temperature and relative humidity known not to influence the results.

• • Where the monograph specifies that the specimen under test is hygroscopic, use a dry syringe to inject an appropriate volume of methanol, or other suitable solvent, accurately measured, into a tared container, and shake to dissolve the specimen.

• • Using the same syringe, remove the solution from the container and transfer it to a titration vessel prepared as directed for procedure.

• • Repeat the procedure with a second portion of methanol, or other suitable solvent, accurately measured.

• • Add this washing to the titration vessel, and immediately titrate.

• • Determine the water content, in mg, of a portion of solvent of the same total volume as that used to dissolve the specimen and to wash the container and syringe, as directed for standardization of water solution for residual titrations, and subtract this value from the water content, in mg, obtained in the titration of the specimen under test.

• • Dry the container and its closure at 100ºC for 3 hours. Allow to cool in a desiccator and weight.

• • Determine the weight of specimen tested form the difference in weight from the initial weight of the container.

• • Standardization of the Reagent:

• • Place enough methanol or other suitable solvent in the titration vessel to cover the electrodes, and add sufficient reagent to give the characteristic endpoint color, or 100 ± 50 microamperes of direct current at about 200mv of applied potential.

• • For determination of trace amounts of water (less than 1 %), sodium tartrate may be used as a convenient water reference substance.

• • Quickly add 150 to 350 mg of sodium tartrate (C₄H₄O₆Na₂, 2H₂O), accurately weighed by difference and titrate to the end point.

• • The water equivalence factor F in mg of water per ml of reagent is given by the formula.

2(18.02/230.08) (W/V)

• • In which 18.02 and 230.08 are the molecular weights of water and sodium tartrate dehydrate respectively; W is the weight in mg of sodium tartrate dehydrate, and V is the volume in ml of the reagent consumed in the second titration.

• • For the precise determination of significant amounts of water (1 % or more), use purified water as the reference substance.

• • Quickly add between 25 and 250 mg of water, accurately weighed by difference form a weighing pipet or from a precalibrated syringe or micro pipet, the amount taken being governed by the reagent strength and the burette size.

• • Titrate to the endpoint. Calculate the water equivalence factor, F in mg of water per ml of reagent by the formula.

W/V

• • In which W is the weight in mg of the water and V is the volume in ml of the reagent required.

• Procedure For Moisture Content Determination:

  • Unless otherwise specified, transfer about 50 ml of methanol or other suitable solvent to the titration vessel, and titrate with the reagent to the electrometric or visual endpoint to consume any moisture that may be present (Disregard the volume consumed, since it does not enter into the calculations).

• • Quickly add the test preparation mix and again titrate with the reagent to the electrometric or visual endpoint calculates the water content of the specimen in mg taken by the formula;

SF

• • In which S is the volume in ml of the reagent consumed in the second titration; and F is the water equivalence factor of the reagent.

• • Method Ib (Residual Titration) for Water Content

• • Apparatus, Reagent and Test Preparation – use method Ia.

• • Standardization of Water Solution for Residual Titration:

• • Prepare a water solution by diluting 2 ml of water with methanol or other suitable solvent to 1000 ml. standardize this solution by titrating 25.0 ml with the reagent.

• • Previously standardize as directed under standardization of the reagent.

• • Calculate the water content, in mg per ml, of the water solution taken by the formula:

VF/25

• • In which V is the volume of the reagent consumed and F is the water equivalence factor of the reagent.

• • Determine the water content of the water solution weekly, and standardize the reagent against it periodically as needed.

• • Procedure:

• • Where the individual monograph specifies that the water content is to be determined by method Ib.

• • Transfer 35 to 40 ml of methanol or other suitable solvent to the titration vessel, and titrate with the reagent to the electrometric or visual endpoint.

• • Quickly add the test preparation, mix and add an accurately measured excess of the reagent.

• • Allow sufficient time for the reaction to reach completion, and titrate the unconsumed reagent with standardized water solution to the electrometric or visual endpoint calculate the water content of the specimen in mg taken by the formula:

F(X’-XR)

• • In which F is the water equivalence factor of the reagent, X’ is the volume in ml of the reagent added after introduction of the specimen, X is the volume in ml of standardization water solution required to neutralize the unconsumed reagent, and R is the ratio, V/25 (ml reagent/ ml water solution), determined from the standardization of water solution for residual titration.

• Method Ic (Coulometric Titration) for Water Content Determination

  • Principle

• • The Karl Fischer reaction is used in the Coulometric determination of water.

• • Iodine however is not added in the form of a volumetric solution but is produced in an iodide containing solution by anodic oxidation.

• • The reaction cell usually consists of large anode compartment and a small cathode compartment that are separated by a diaphragm.

• • Other suitable types of reaction cells (e.g. without diaphragms) may also be used.

• • Each compartment has platinum electrode that conducts current through the cell.

• • Iodine which is produced at the anode electrode, immediately reacts with water present in the compartment when all the water has been consumed, an excess of iodine occurs, which usually is detected electrometrically, thus indicating the endpoint moisture is eliminated from the system by pre-electrolysis.

• • Changing the Karl Fischer solution after each determination is not necessary since individual determinations can be carried out in succession in the same reagent solution.

• • A requirement for this method is that each component of the test specimen is compatible with the other components, and no side reactions take place.

• • Samples are usually transferred into the vessel as solutions by means of injection through a septum.

• • Gases can be introduced into the cell is not recommended, unless elaborate precautions are taken, such as working in a glove box in an atmosphere of dry inert gas. Control of the system may be monitored by measuring the amount of baseline drift.

• • This method is particularly suited to chemically inert substances like hydrocarbons, alcohols and ethers.

• • In comparison with the volumetric Karl Fischer titration, Coulometry is a micro-method.

• • Apparatus for Coulometric Titration

• • Any commercially available apparatus consisting of an absolute tight system fitted with the necessary electrodes and a magnetic stirrer is appropriate.

• • The instruments microprocessor controls the analytical procedure and displays the results.

• • Calibration of the instrument is not necessary, as the current consumed can be measured absolutely.

• • Reagent- see Reagent Under Method Ia

• • Test Preparation

• • Where the specimen is a soluble solid, dissolve an appropriate quantity, accurately weighed in anhydrous methanol or other suitable solvents.

• • Liquids may be used as such or as accurately prepared solutions in appropriate anhydrous solvents.

• • Where the specimen is an insoluble solid, the water may be extracted using a suitable anhydrous solvent form which an appropriate quantity, accurately weighed may be injected into the analyte solution.

• • Alternatively an evaporation technique may be used in which water is released and evaporated by heating the specimen in a tube in a stream of dry inert gas, this gas being then passed into the cell.

• • Procedure

• • Using a syringe quickly inject the test preparation accurately measured and estimated to contain0.5 to 5 mg of water, or as recommended by the instrument manufacturer into the analyte mix and perform the Coulometric titration to the electrometric endpoint.

• • Read the water content of the test preparation directly from the instruments display and calculate the percentage that is present in the substance.

• • Perform a blank determination and make any necessary corrections.

• Method II (AZEOTROPIC – TOLUENE DISTILLATION)

  • Apparatus

• • Use a 500 ml glass flask A connected by means of a trap B to a reflux condenser C by ground glass joints.

• • The critical dimensions of the parts of the apparatus are as follows.

• • The connecting tube D is 9 to 11 mm in internal diameter.

• • The trap is 235 to 240 mm in length. The condenser, if the straight tube type is approximately 400 mm in length and not less than 8 mm in bore diameter.

• • The receiving tube E has a 5 ml capacity, and its cylindrical portion, 146 to 156 mm in length, is graduated in 0.1 ml subdivisions so that the error of reading is not greater than 0.05 ml for nay indicated volume.

• • The source of heat is preferably an electric heater with rheostat control or an oil bath.

• • The upper portion of the flask and the connecting tube may be insulated.

• • Clean the receiving tube and the condenser with chromic acid cleansing mixture, thoroughly rinse with water, and dry in an oven.

• • Prepare the toluene to be used by first shaking with a small quantity of water separating the excess water, and distilling the toluene.

• • Procedure

• • Place in the dry flask a quantity of the substance weighed accurately to the nearest centigram, which is expected to yield 2 to 4 ml of water.

• • If the substance is of pasty character weigh it in a boat of metal foil of a size that will just pass through the neck of the flask.

• • If the substance is likely to cause bumping add enough dry washed sand to cover the bottom of the flask, or a number of capillary melting point tubes, about 100 mm in length sealed at the upper end.

• • Place about 200 ml of toluene in the flask. Connect the apparatus and fill the receiving tube E with toluene poured through the top of the condenser.

• • Heat the flask gently for 15 minutes and when the toluene begins to boil distill at the rate of about 2 drops per second until most of the water has passed over, then increase the rate of distillation to about 4 drops per second.

• • When the water has apparently all distilled over, rinse the inside of the condenser tube with toluene while brushing down the tube with a tube brush attached to a copper wire and saturated with toluene.

• • Continue the distillation for 5 minutes, then remove the heat, and allow the receiving tube to cool to room temperature.

• • If any droplets of water adhere to the walls of the receiving tube, scrub them down with a brush consisting of a rubber band wrapped around a copper wire and wetted with toluene.

• • When the water and toluene have separated completely, read the volume of water and calculate the percentage that was present in the substance.

• Method III (Gravimetric) for Water Content Determination

  • Procedures for chemicals proceed as directed in the individual STP.

• • Preparing the chemical as directed under loss on drying procedure.

• • Procedure for Biologics:

• • Proceed as directed in the individual STP.

• • Procedure for Articles of botanical origin

• • Place about 10 gm. of the drug prepared as directed (for more details refer USP, Methods of analysis under articles of botanical origin (561)] and accurately weighed in a tared evaporating dish.

• • Dry at 105ºC for 5 hours and weigh. Continue the drying and weighing at 1-hour intervals until the difference between two successive weighing corresponds to not more than 0.25 %.

• • As per BP/ph. Eur.

• • Use method IA unless otherwise directed.

• • Method I

• • Apparatus

• • The titration vessel of about 60 ml capacity is fitted with 2 platinum electrodes a nitrogen inlet tube, a stopper which accommodates the burette tip, and a vent tube protected by a desiccant.

• • The substance to be examined is introduced through a side arm which can be closed by a ground stopper. Stirring is effected magnetically or by means of a stream of dried nitrogen passed through the solution during the titration.

• • The endpoint is determined by amperometry.

• • A suitable circuit consists of a potentiometer of about 2000 W connected across a 1.5 V battery to supply a variable potential.

• • This potential is adjusted so that an initial low current passes through the platinum electrodes connected in series with a microammeter.

• • On adding the reagent the needle of the microammeter shows a deflection but returns immediately to its starting position.

• • At the end of the reaction a deflection is obtained which persists for not less than 30s.

• • Use the Karl Fischer reagent VS after determination of the water equivalent.

• • The reagent and solutions used must be kept anhydrous and precautions must be taken throughout to prevent exposure so atmospheric moisture.

• • The Karl Fischer reagent VS is protected from light, preferably stored in a bottle to which is fitted an automatic burette.

• • The composition of commercially available iodosulphurous reagents often differs from that of Karl Fischer reagent VS (iodosulphurous reagent R) by the replacement of pyridine with various other basic compounds.

• • The use of these reagents must previously be validated in order to verify in each individual case, the stoichiometry and the absence of incompatibility between the substance under test and the reagent. (Refer BP, General Notices part II 1.1. General Statements).

• • Method Ia

• • Unless otherwise prescribed, add about 50 ml of anhydrous methanol R or the solvent prescribed in the monograph to the titration vessel and titrate to the amperometric end point with the Karl Fischer reagent VS.

• • Quickly transfer the prescribed amount of the substance to be examined to the titration vessel.

• • Stir for 1 min and titrate again to the amperometric endpoint using Karl Fischer VS.

• • Method Ib

• • Add about 10 ml of anhydrous methanol R or the solvent prescribed in the STP to the titration vessel and titrate to the amperometric endpoint with Karl Fischer reagent VS.

• • Quickly transfer the prescribed amount of the substance to be examined in a suitable state of division followed by an accurately measured volume of Karl Fischer reagent VS, sufficient to give an excess of about 1 ml of the volume prescribed in the monograph.

• • Allow the stoppered flask to stand protected from light for 1 min or the time prescribed in the monograph, stirring form time to time.

• • Titrate the excess of Karl Fischer reagent VS until the initial low current is again obtained, using anhydrous methanol R or the solvent prescribed in the monograph, to which has been added an accurately known amount of water R equivalent to about 2.5g/l.

• • Method II Determination of Water by Distillation

• • Apparatus

• • The apparatus (see figure) consists of a glass flask (A) connected by a tube (D) to a cylindrical tube (B) fitted with a graduated receiving tube (E) and reflux condenser (C).

• • The receiving tube (E) is graduated in 0.1 ml. the source of heat is preferably an electric heater with rheostat control or an oil bath.

• • The upper portion of the flask and the connecting tube may be insulated.

• • Method

• • Clean the receiving tube and the condenser of the apparatus, thoroughly rinse with water, and dry.

• • Introduce 200 ml of toluene R and about 2 ml of water R into the dry flask.

• • Distil for 2 hr, then allow to cool for about 30 min and read the water volume of the nearest 0.05 ml.

• • Place in the flask a quantity of the substance, weighed with an accuracy of 1 percent, expected to give about 2 ml to 3 ml of water.

• • If the substance has a pasty consistency, weigh it in a boat of metal foil.

• • Add a few pieces of porous material and heat the flask gently for 15 min.

• • When the toluene begins to boil, distil at the rate of about two drops per second until most of the water has distilled over, and then increase the rate of distillation to about four drops per second.

• • When the water has all distilled over, rinse the inside of the condenser tube with toluene R. continue the distillation for 5 min, remove the heat, allow the receiving tube to cool to room temperature and dislodge any droplets of water which adhere to the walls of the receiving tube.

• • When the water and toluene have completely separated, read the volume of water and calculate the content present in the substance as milliliter per kilogram, using the formula:

1000(n₂ – n₁)

• • n₁ = the number of the milliliters of water obtained in the first distillation

• • n₂ = the total number of milliliters of water obtained in the 2 distillations.

• • Method III (Coulometric Titration)

• • Moisture is eliminated from the system by pre-electrolysis. Individual determinations can be carried out successively in the same reagent solution, under the following conditions.

• • Each components of the test mixture is compatible with the other components,

• • No other reactions take place,

• • The volume and the water capacity of the electrolyte reagent are sufficient.

• • Coulometric titration is restricted to the quantitative determination of small amounts of water, a range of 10 µg up to 10 mg of water is recommended.

• • Accuracy and precision of the method are predominantly governed by the extent to which atmospheric moisture is excluded from the system. Control of the system must be monitored by measuring the amount of baseline drift.

• • Apparatus

  • The apparatus consist of a reaction cell, electrodes and magnetic stirrer.

• • The reaction cell consists of a large anode compartment and a smaller cathode compartment.

• • Depending on the design of the electrode, both compartments can be separated by a diaphragm.

• • Each compartment contains a platinum electrode. Liquid or solubilized sample are introduced through a septum, using a syringe.

• • Alternatively an evaporating technique may be used in which the sample is heated in a tube (oven) and the water is evaporated and carried into the cell by means of a stream of dry inert gas.

• • The introduction of solid samples into the cell should in general be avoided.

• • However if it has to be done it is effected through a sealable port, appropriate precautions must be taken to avoid the introduction of moisture from air, such as working in a glove box in an atmosphere of dry inert gas.

• • The analytical procedure is controlled by a suitable electronic device, which also displays the results.

• • Method

• • Fill the compartments of the reaction cell with electrolyte reagent for the micro determination of water R according to the manufacturer’s instructions and perform the Coulometric titration to be stable end point.

• • Introduce the prescribed amount of the substance to be examined into the reaction cell, stir for 30 s, if not otherwise indicated in the monograph, and titrate again to a stable end point.

• • In case an oven is used, the prescribed sample amount is introduced into the tube and heated.

• • After evaporation of the water from the sample into the titration cell, the titration is started.

• • Read the value from the instruments output and calculate if necessary the percentage or amount of water that is present in the substance.

• • When appropriate to the type of sample and the sample preparation, perform a blank titration.

• • Verification of the Accuracy

  • Between two successive sample titration, introduce an accurately weighed amount of water in the same order of magnitude as the amount of water in the sample, either as water R or in the form of standard solution for the micro determination of water R, and perform the Coulometric titration.

• • The recovery rate is within the range from 97.5 % to 102.5 % for an addition of 1000 µg of H₂O and in the range from 90.0 % to 110.0 % for the addition of 100 µg of H₂O.

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