2.4. LIMIT TESTS - DrugFuture

1 EUROPEAN PHARMACOPOEIA LIMIT TESTS01/2008 AMMONIUMU nlessotherwiseprescribed, ADissolvetheprescribedquantityofthesubst ancetobeexaminedin 14 mL ofwater Rin a test-tube, make alkaline if necessary bythe addition ofdilute sodium hydroxide solution Rand diluteto 15 mL withwater tetraiodomercurate solution R. Prepare a standardby mixing 10 mL ofammonium standard solution (1 ppmNH4)Rwith 5 mL ofwater Rand mL ofalkaline potassiumtetraiodomercurate solution R. Stopper the 5 min, any yellow colour in the test solution is not moreintense than that in the BIn a 25 mL jar fitted with a cap, place the prescribed quantity ofthe finely powdered substance to be examined and dissolve orsuspend in 1 mL ofwater R.

2 Add g ofheavy magnesiumoxide R. Close immediately after placing a piece ofsilvermanganese paper R5 mm square, wetted with a few drops ofwater R, under the polyethylene cap. Swirl, avoiding projectionsof liquid, and allow to stand at 40 C for 30 min. If the silvermanganese paper shows a grey colour, it is not more intensethan that of a standard prepared at the same time and in thesame manner using the prescribed volume ofammoniumstandard solution (1 ppm NH4)R,1mLofwater Rand gofheavy magnesium oxide ARSENICMETHOD AThe apparatus (see Figure ) consists of a 100 mL conicalflask closed with a ground-glass stopper through which passesa glass tube about 200 mm long and of internal diameter 5 ,and15mmfromitstipisalateralorifice2mmto 3mmin diameter.

3 When the tube is in position in the stopper, thelateral orifice should be at least 3 mm below the lower surfaceof the stopper. The upper end of the tube has a perfectly flat, tube of the same internal diameter and 30 mm long, witha similar flat ground surface, is placed in contact with the first,and is held in position by two spiral springs. Into the lowertube insert 50 mg to 60 mg oflead acetate cotton R,looselypacked,orasmallplugofcottonanda rolledpieceofleadacetate paper Rweighing 50 mg to 60 mg. Between the flatsurfaces of the tubes place a disc or a small square ofmercuricbromide paper Rlargeenoughtocovertheorificeofthetube(1 5 mm 15 mm).In the conical flask dissolve the prescribed quantity of thesubstance to be examined in 25 mL ofwater R,orinthecaseofa solution adjust the prescribed volume to 25 mL withwater 15 mL ofhydrochloric acid R, chloridesolution Rand 5 mL ofpotassium iodide solution R, allowto stand for 15 min and introduce 5 g ofactivated zinc the two parts of the apparatus immediately andimmerse the flask in a bath of water at a temperature such thata uniform evolution of gas is maintained.

4 Prepare a standardinthesamemanner,using1mLofarseni c standard solution(1 ppm As) R,dilutedto25mLwithwater not less than 2 h the stain produced on the mercuricbromide paper in the test is not more intense than that in BIntroduce the prescribed quantity of the substance to beexamined into a test-tube containing 4 mL ofhydrochloricacid Rand about 5 mg ofpotassium iodide Rand add 3 mL ofhypophosphorous reagent 15 min, shaking occasionally. Prepare a standard in thesame manner, using mL ofarsenic standard solution(10 ppm As) heating on the water-bath, any colour in the test solutionis not more intense than that in the -Apparatus for LIMIT test A for arsenicDimensions in millimetres01/2008 CALCIUMAll solutions used for this test shouldbepreparedwithdistilledwater mL ofalcoholic calcium standard solution(100 ppm Ca) R,add1mLofammonium oxalate solution 1 min, add a mixture of 1 mL ofdilute acetic acid Rand15 mL of a solution containing the prescribed quantity of thesubstance to be examined and shake.

5 Prepare a standard in thesame manner using a mixture of 10 mL of aqueouscalciumstandard solution (10 ppm Ca) R, 1 mL ofdilute acetic acid Rand 5 mL ofdistilled water 15 min, any opalescence in the test solution is not moreintense than that in the CHLORIDESTo 15 mL of the prescribed solution add 1 mL ofdilute nitricacid Rand pour the mixture as a single addition into a test-tubecontaining 1 mL ofsilver nitrate solution in the same manner using 10 mL ofchloride standardsolution (5 ppm Cl) Rand 5 mL ofwater against a black standing for 5 min protected from light, any opalescence inthe test solution is not more intense than that in the Notices (1) apply to all monographs and other FluoridesEUROPEAN PHARMACOPOEIA FLUORIDESF igure Apparatus for LIMIT test for fluoridesDimensions in millimetresIntroduce into the inner tube of the apparatus (seeFigure ) the prescribed quantity of the substance to beexamined, g of acid-washedsand Rand 20 mL of a mixtureof equal volumes ofsulfuric acid Randwater containingtetrachloroethane Rmaintained at its boilingpoint (146 C).

6 Heat the steam generator and distil, collectingthe distillate in a 100 mL volumetric flask containing M sodium hydroxideand mL ofphenolphthaleinsolution R. Maintain a constant volume (20 mL) in the tubeduring distillation and ensure that the distillate remainsalkaline, M sodium hydroxideif necessary. Dilutethedistillateto100mLwithwater R(test solution). Preparea standard in the same manner by distillation, using 5 mLoffluoride standard solution (10 ppm F) Rinstead of thesubstance to be examined. Into two glass-stoppered cylindersintroduce 20 mL of the test solution and 20 mL of the standardand 5 mL ofaminomethylalizarindiacetic acid reagent 20 min, any blue colour in the test solution (originally red)is not more intense than that in the MAGNESIUMTo 10 mL of the prescribed solution add g ofdisodiumtetraborate ,ifnecessary, usingdilute hydrochloric acid Rordilute sodiumhydroxide solution R.

7 Shake with 2 quantities, each of 5 mL,of a 1 g/L solution ofhydroxyquinoline Rinchloroform R,for 1 min each time. Allow to stand. Separate and Rand mL oftriethanolamine , if necessary, to pH to pH Add 4 mL of thesolution of hydroxyquinoline in chloroform, shake for 1 min,allow to stand and separate. Use the lower layer for a standard in the same manner using a mixture of 1 mLofmagnesiumstandardsolution(10ppmMg)Ra nd 9 mL ofwater colour in the solution obtained from the substance to beexamined is not more intense than that in the MAGNESIUM ANDALKALINE-EARTH METALSTo 200 mL ofwater Radd g ofhydroxylaminehydrochloride R,10mLofammonium chloride buffer solutionpH R, 1 mL M zinc sulfateand about 15 mg ofmordant black 11 triturate M sodium edetateuntil the violet colour changes tofull blue.

8 To the solution add the prescribed quantity of thesubstance to be examined dissolved in 100 mL ofwater Ror usethe prescribed solution. If the colour of the solution changesto violet, titrate M sodium edetateuntil the full bluecolour is again volume M sodium edetateused in the secondtitration does not exceed the prescribed HEAVY METALST hemethodsdescribedbelowrequiretheuseofth ioacetamidereagent ,sodium sulfide solution R1( mL) is usually suitable. Since TESTS prescribed inmonographs have been developed usingthioacetamidereagent R,ifsodium sulfide solution R1is used instead, it isnecessary to include also for methods A, B and H a monitorsolution, prepared from the quantity of the substance to beexamined prescribed for the test, to which has been added thevolume of lead standard solution prescribed for preparation ofthe reference solution.

9 The test is invalid if the monitor solutionis not at least as intense as the reference ATest solution. 12 mL of the prescribed aqueous solution of solution (standard). A mixture of 10 mL ofleadstandard solution (1 ppm Pb) Rorlead standard solution(2 ppm Pb) R, as prescribed, and 2 mL of the prescribedaqueous solution of the substance to be Rand 2 mL of theprescribed aqueous solution of the substance to be each solution, add 2 mL ofbuffer solution pH to mL ofthioacetamide reagent R. Mix the solutions after 2 suitability: the reference solution shows a slight browncolour compared to the blank : any brown colour in the test solution is not more intensethan that in the reference the information section on general monographs (cover pages)