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Silver nitrate   EUROPEAN PHARMACOPOEIA 5.0

The chromatographic procedure may be carried out using:

— a non-metallic column 0.25 m long and 4.6 mm in internaldiameter packed with a suitable anion-exchange resin(30 µm to 50 µm ),

— as mobile phase at a flow rate of 1.2 ml/min a solutionprepared as follows: dissolve 0.508 g of  sodiumcarbonate R and 0.05 g of  sodium hydrogen carbonate R

in water R  and dilute to 1000 ml with the same solvent,— a conductivity detector,

— a loop injector.

Inject 25 µl of the test solution and 25 µl of the referencesolution. When the chromatograms are recorded in theprescribed conditions, the retention times are: sulphateabout 8 min and chloride about 4 min.

In the chromatogram obtained with the test solution thearea of any peak corresponding to sulphate is not greaterthan that of the corresponding peak in the chromatogramobtained with the reference solution (4.0 per cent calculatedas sodium sulphate).

Iron ( 2.4.9). Dilute 2 ml of solution S to 40 ml with  water R.

10 ml of the solution complies with the limit test for iron(400 ppm).

Heavy metals ( 2.4.8 ). To 20 ml of solution S, add 50 mg of hydroxylamine hydrochloride R and 1 ml of  concentrated ammonia R. Adjust to pH 3.5 by adding  dilute ammonia R2 ,monitoring the pH potentiometrically. Dilute to 25 ml withwater R. 12 ml of the solution complies with limit test A forheavy metals (25 ppm). Prepare the standard using  lead 

 standard solution (1 ppm Pb) R .

Loss on ignition. Not more than 25.0 per cent, determinedon 0.200 g in a platinum crucible by heating at 100 °C to105 °C for 1 h and then at 1000 °C for 2 h.

ASSAY

To the residue obtained in the test for loss on ignition add0.2 ml of  sulphuric acid R and a quantity of  alcohol Rsufficient to moisten the residue completely. Add 6 ml of hydrofluoric acid R and evaporate to dryness at 95 °C to105 °C, taking care to avoid loss from sputtering. Wash theinside of the crucible with 6 ml of  hydrofluoric acid R andevaporate to dryness again. Ignite at 900 °C, allow to coolin a desiccator and weigh. The difference between the massof the final residue and that of the mass obtained in thetest for loss on ignition corresponds to the mass of SiO 2 inthe test sample.

01/2005:0009

SILVER NITRATE

Argenti nitras

AgNO3   M r 169.9

DEFINITION

Silver nitrate contains not less than 99.0 per cent and not more than the equivalent of 100.5 per cent of AgNO 3.

CHARACTERS

A white, crystalline powder or transparent, colourless

crystals, very soluble in water, soluble in alcohol.

IDENTIFICATION

A. 10 mg gives the reaction of nitrates ( 2.3.1).

B. 10 mg gives the reaction of silver ( 2.3.1).

TESTS

Solution S. Dissolve 2.0 g in water R and dilute to 50 mlwith the same solvent.

Appearance of solution. Solution S is clear ( 2.2.1) andcolourless ( 2.2.2, Method II ).

Acidity or alkalinity. To 2 ml of solution S add 0.1 ml of bromocresol green solution R. The solution is blue. To

2 ml of solution S add 0.1 ml of  phenol red solution R. Thesolution is yellow.

Foreign salts. To 30 ml of solution S, add 7.5 ml of  dilutehydrochloric acid R, shake vigorously, heat for 5 min ona water-bath and filter. Evaporate 20 ml of the filtrate todryness on a water-bath and dry at 100-105 °C. The residueweighs not more than 2 mg (0.3 per cent).

Aluminium, lead, copper and bismuth. Dissolve 1.0 g in amixture of 4 ml of  concentrated ammonia R  and 6 ml of water R. The solution is clear ( 2.2.1) and colourless ( 2.2.2,

 Method II ).

ASSAY

Dissolve 0.300 g in 50 ml of  water R and add 2 ml of  dilutenitric acid R  and 2 ml of   ferric ammonium sulphate solution R2 . Titrate with 0.1 M ammonium thiocyanateuntil a reddish-yellow colour is obtained.

1 ml of  0.1 M ammonium thiocyanate   is equivalent to16.99 mg of AgNO3.

STORAGE

Store in a non-metallic container, protected from light.

01/2005:1470

SIMETICONE

SimeticonumDEFINITION

Simeticone is prepared by incorporation of 4 per cent to7 per cent silica into poly(dimethylsiloxane) with a degree of polymerisation between 20 and 400. Simeticone contains90.5 per cent to 99.0 per cent of poly(dimethylsiloxane).

PRODUCTION

Poly(dimethylsiloxane) is obtained by hydrolysisand polycondensation of dichlorodimethylsilane andchlorotrimethylsilane and the silica is modified at the surfaceby incorporation of methylsilyl groups.

CHARACTERSA viscous, greyish-white, opalescent liquid, practicallyinsoluble in water, very slightly soluble to practicallyinsoluble in ethanol, practically insoluble in methanol, partlymiscible with ethyl acetate, with methylene chloride, withmethyl ethyl ketone and with toluene.

IDENTIFICATION

A. Examine by infrared absorption spectrophotometry( 2.2.24). Absorption maxima are observed at 2964 cm−1,2905 cm−1, 1412 cm−1, 1260 cm−1 and 1020 cm−1.Examine the substances as thin films between  sodiumchloride R plates.

B. Heat 0.5 g in a test-tube over a small flame until white

fumes begin to appear. Invert the tube over a secondtube containing 1 ml of a 1 g/l solution of  chromotropic acid, sodium salt R in  sulphuric acid R  so that the fumesreach the solution. Shake the second tube for about 10 sand heat on a water-bath for 5 min. The solution is violet.

2412   See the information section on general monographs (cover pages)

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EUROPEAN PHARMACOPOEIA 5.0   Simvastatin

C. The residue obtained in the test for silica under Assay,gives the reaction of silicates ( 2.3.1).

TESTS

Acidity. To 2.0 g add 25 ml of a mixture of equal volumes of ethanol R and  ether R previously neutralised to 0.2 ml of bromothymol blue solution R1, and shake. Not more than3.0 ml of  0.01 M sodium hydroxide  is required to change thecolour of the solution to blue.

Defoaming activity

 Foaming solution. Dissolve 5.0 g of  docusate sodium R in1 litre of  water R (warm to 50 °C if necessary).

 Defoaming solution. To 50 ml of  methyl ethyl ketone Radd 0.250 g of simeticone, warm to not more than 50 °Cwith shaking.

Into a 250 ml cylindrical tube about 5 cm in diameterintroduce 100 ml of foaming solution and 1 ml of defoamingsolution. Close tightly and fix the tube on a suitableoscillating shaker that complies with the followingconditions:

— 250 to 300 oscillations per minute,

— angle of oscillation of about 10°,

— oscillation radius of about 10 cm.

Shake for 10 s and record the time between the end of theshaking and the instant the first portion of foam-free liquidsurface appears.

This duration does not exceed 15 s.

Mineral oils. Place 2.0 g in a test-tube and examine inultraviolet light at 365 nm. The fluorescence is not moreintense than that of a solution containing 0.1 ppm of  quinine

 sulphate R  in  0.005 M sulphuric acid  examined in the sameconditions.

Phenylated compounds. Dissolve 5.0 g with shaking in10.0 ml of  cyclohexane R. Determine the absorbance of the solution between 200 nm and 350 nm ( 2.2.25 ) usingcyclohexane R as the compensation liquid. The correctedabsorbance (absorbance measured at the maximum between250 nm and 270 nm minus the absorbance measured at 300 nm) is not greater than 0.2.

Heavy metals. Mix 1.0 g with  methylene chloride R anddilute to 20 ml with the same solvent. Add 1.0 ml of a freshlyprepared 0.02 g/l solution of  dithizone R in  methylenechloride R, 0.5 ml of  water R and 0.5 ml of a mixture of 1 volume of  dilute ammonia R2  and 9 volumes of a 2 g/lsolution of  hydroxylamine hydrochloride R. At the sametime, prepare a standard as follows: to 20 ml of  methylenechloride R add 1.0 ml of a freshly prepared 0.02 g/l solutionof  dithizone R  in  methylene chloride R, 0.5 ml of  lead 

 standard solution (10 ppm Pb) R  and 0.5 ml of a mixture of 1 volume of  dilute ammonia R2  and 9 volumes of a 2 g/lsolution of  hydroxylamine hydrochloride R. Immediatelyshake each solution vigorously for 1 min. Any red colourin the test solution is not more intense than that in thestandard (5 ppm).

Volatile matter. Not more than 1.0 per cent, determined on1.00 g by heating in an oven at 150 °C for 2 h. Carry out thetest using a dish 60 mm in diameter and 10 mm deep.

ASSAY

Silica. Not more than 7 per cent, determined on not lessthan 20.0 mg. Heat the substance to be examined to 800 °Cincreasing the temperature by 20 °C/min under a current of  nitrogen R  at a flow rate of 200 ml/min and weigh theresidue (silica).

Dimeticone

Test solution. Place about 50 mg ( E ) in a screw-capped125 ml cylindrical tube, add 25.0 ml of  toluene R, swirlmanually to disperse and add 50 ml of  dilute hydrochloric acid R, close the tube and place on a vortex mixer; shakefor 5 min. Transfer the contents of the tube to a separatingfunnel, allow to settle and transfer 5 ml of the upper layerto a screw-capped test tube containing 0.5 g of  anhydrous

 sodium sulphate R. Cap and shake vigorously manually.Centrifuge to obtain a clear test solution.

 Reference solution. Introduce about 0.20 g of dimeticone CRS  in 100.0 ml of  toluene R. Prepare thereference solution in the same way as for the test solution,using 25.0 ml of the dimeticone solution obtained above.Prepare a blank by shaking 10 ml of  toluene R with 1 g of anhydrous sodium sulphate R. Centrifuge the resultingsuspension.

Record the infrared absorption spectra for the test solutionand the reference solution in 0.5 mm cells, from 1330 cm−1

to 1180 cm−1, and determine the absorbance of the band at 1260 cm−1 ( 2.2.24).

Calculate the percentage content of dimeticone using theexpression:

 AM   =   absorbance of the test solution,

 AE   =   absorbance of the reference solution,

C    =   concentration of the reference solution, inmilligrams per millilitre,

 E    =   mass of the substance to be examined, inmilligrams.

01/2005:1563

SIMVASTATIN

Simvastatinum

C25H38O5   M r 418.6

DEFINITION

Simvastatin contains not less than 97.0 per cent and not more than the equivalent of 102.0 per cent of (1S ,3 R,7S ,8S ,8a R)-8-[2-[(2 R,4 R)-4-hydroxy-6-oxotetrahydro-2 H -pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl2,2-dimethylbutanoate, calculated with reference to the driedsubstance. A suitable antioxidant may be added.

CHARACTERS

A white or almost white, crystalline powder, practicallyinsoluble in water, very soluble in methylene chloride, freelysoluble in alcohol.

General Notices (1) apply to all monographs and other texts   2413