Limit test for chlorides

To 2 g of niclosamide add a mixture of 1.2 mL of acetic acid and 40 mL water, boil for 2 min, cool and filter. Two milliliters of the filtrate diluted to 15 mL with water complies with the limit test for chlorides (500 ppm) [6]. 

The limit test for chlorides is based on its precipitation with silver nitrate in the presence of dilute HN03, and comparing the opalescence produced due to the formation of AgCl with a standard opalescence achieved with a known quantity of Cl ions. 

Aluminium Hydroxide Gel Dissolve 0.5 g in 5 ml dil. HN03, boil, cool, dilute to 100 ml with DW and filter 2.5 ml used for the test. Complies with limit test for chlorides. 

Bephenium Hydroxy-napthoate Boil 2.5 g with 100 ml DW, cool in ice and filter to 20 ml of filtrate, add 10 ml dil. HN03 shake and filter. Test with the filtrate. Complies with limit test for chlorides. 

Frusemide Shake 1.0 g with 40 ml DW for 5 minutes and filter. Test with filtrate as stated in 5 above. Complies with the limit test for chlorides (250 ppm). 

Isocarboxazid Boil 0.5 g with 5 ml H202 soln. (30%) and 10 ml NaOH soln. (20% w/v in DW) for 2 minutes. Cool, neutralize to litmus with HN03 and add sufficient DW to produce 40 ml. Test with the resulting solution. Complies with limit test for chlorides (25 ppm). 

Chloride. To 0.250 g of the substance under test, add 10 mL of water R and shake strongly. Filter, rinse the filtrate with 5 mL of water R, and dilute to 15 mL with water R. The combined filtrates comply with the limit test for chloride (not more than 200 ppm). 

The limit test for chlorides is based on the same chemistry as the identification test for chlorides, 3.16. Chlorides. The opalescence given by precipitation of the chloride present in the substance to be examined with silver is compared to the opalescence given in a similar precipitation of a chloride standard of known concentrahon. 

Potassium Chloride 20 ml of a 10% w/v solution in C02 free DW and carry out the test as stated in 2 above. Complies with limit test for iron. 

Acid radical impurities constitute a serious but unavoidable source of impurities in a large number of pharmaceutical chemicals. However, the two most commonly found acid radical impurities are chloride (Cl ) and sulphate (S042 ) that evidently arise from the inevitable use of raw tap-water in various manufacturing operations. As these two acid radical impurities are found in abundance due to contamination, the Pharmacopoeia categorically stipulates limit tests for them which after due minor modifications are applicable to a number of pharmaceutical substances. 

Theory The limit test for sulphates is based upon its precipitation as barium sulphate in the presence of barium chloride, hydrochloric acid and traces of barium sulphate. In this combination, hydrochloric acid exerts its common ion effect whereas traces of BaS04 aids in the rapid and complete precipitation by seeding. Thus, the opalescence caused by the sample is compared immediately with a standard turbidity produced with a known amount of the S042 ion. 

Time Limits Unless otherwise specified, allow 5 min for a reaction to take place when conducting limit tests for trace impurities such as chloride or iron. 

Nonvolatile Residue Transfer 4 g of sample into a tared dish, add 10 mL of water, and evaporate on a steam bath. Heat the dish at 105° for 1 h, cool in a desiccator, and weigh. Sulfur Compounds Determine as directed in the Sulfate Limit Test under Chloride and Sulfate Limit Tests, Appendix IIIB, using the residue of the following Dissolve 4 g of sample in 40 mL of water, add about 10 mg of sodium carbonate and 1 mL of 30% hydrogen peroxide, and evaporate the solution to dryness on a steam bath. Any turbidity produced does not exceed that shown in a control containing 200 jxg of sulfate (S04) ion. 

Chloride Determine as directed in the Chloride Limit Test under Chloride and Sulfate Limit Tests, Appendix IIIB. Dissolve 1 g of sample in 100 mL of water. Any turbidity produced by a 10-mL portion of this solution does not exceed that shown in a control containing 70 p,g of chloride (Cl) ion. Ferric Iron Dissolve about 5 g of sample, accurately weighed, in a mixture of 100 mL of water and 10 mL of hydrochloric acid in a 250-mL glass-stoppered flask, add 3 g of potassium iodide, shake well, and allow to stand in the dark for 5 min. Titrate any liberated iodine with 0.1IV sodium thiosulfate, using starch TS as the indicator. Each milliliter of 0.1 N sodium thiosulfate is equivalent to 5.585 mg of ferric iron. 

Sulfate Determine as directed in the Sulfate Limit Test under Chloride and Sulfate Limit Tests, Appendix IIIB. Any turbidity produced by a 20-mL portion of the solution prepared for the Chloride Test (above) does not exceed that shown in a control containing 200 pg of sulfate (S04). 

The selectivity of the test is quite limited, even compared to the specificity seen in the identification test for chlorides. In the identification three criteria have to be fulfilled to qualify for a positive reaction. The unknown should give a white (curdled) precipitate formed upon addition of silver nitrate, which is insoluble in dilute nitric acid but redissolves in ammonia. In the limit test 2.4.4. Chlorides any substance capable of giving a white or weakly colored precipitate in dilute nitric acid will give a response like chloride, and this should be remembered in case of an xmexpected result. For the sake of example the following ions and substances are capable of giving a false positive reaction bromide, iodide, bromate, iodate, sulfite, chlorate, oxalate, and benzoate. In addition to this a variety of more complex organic substances are likely to precipitate, for example, alkaloids. 

Comeal organ culture combined with objectively quantifiable assays for comeal epithelial barrier disruption reduces the high variability associated to the subjectively scored Draize Test. The FITC-Dextran retention has been studied as a quantitative evaluation of the comeal epithelial barrier (Lopez et al. 1991) following chemical exposure of bcnzal konium chloride (BAC), Polyquad, and Thimerosal. Sodium dodecyl sulfate (SDS) has also been tested for disruption of the tight junctions via FITC-Dextran retention assay. However, as an objective outcome measure for ocular toxicity, the scoring system is not yet quantitatively comparable for assessment of ocular irritancy to multiple test products. This limitation is similar to surface biotinylation assays. As fluorometry is utilized more extensively in varied laboratories with numerous test chemicals a standardized scoring system can be elicited similar to the familiar Draize Test. 

Lead Determine as directed for Method I in the Atomic Absorption Spectrophotometric Graphite Furnace Method under Lead Limit Test, Appendix IIIB, using a 10-g sample. Oxalate Neutralize 10 mL of a 1 10 aqueous solution with 6 N ammonium hydroxide, add 5 drops of 2.7 N hydrochloric acid, cool, and add 2 mL of calcium chloride TS. No turbidity develops. 

Chloride Content (as Cl) Transfer about 1 g of sample, previously dried in vacuum for 1 h and accurately weighed, into a 250-mL beaker, and add sufficient water to make 100 mL. Equip a pH meter with glass and silver electrodes, and set it on the + millivolt scale. Insert the electrodes and a motor-driven, glass stirring rod into the sample beaker. Add 1 to 2 drops of methyl orange TS. Stir, and add, drop wise, 10% nitric acid until a pink color appears, then add 10 mL in excess. Titrate the solution with 0.1 A silver nitrate to a reading of +1.0 millivolt on the pH meter. Each milliliter of 0.1 A silver nitrate is equivalent to 3.545 mg of chloride. Lead Determine as directed in the APDC Extraction Method under Lead Limit Test, Appendix IIIB. 

Refer to the Arsenic Limit Test, Appendix IIIB. Add 2 mL of potassium iodide TS and 0.5 mL of Stannous Chloride Solution to the Erlenmeyer flask, and continue as directed in the Procedure, beginning with, Allow the mixture to stand for 30 min at room temperature. .. but use 6.0 mL, rather than 3.0 mL, of Standard Arsenic Solution in the preparation of the standard. 

Clarity and Color of Solution A 1 10 aqueous solution is colorless and has no more turbidity than a standard mixture prepared as follows Dilute 0.2 mL of Standard Chloride Solution (see Chloride and Sulfate Limit Tests, Appendix IIIB) with water to 20 mL add 1 mL of 1 3 nitric acid, 0.2 mL of a 1 50 dextrin solution, and 1 mL of a 1 50 silver nitrate solution mix and allow to stand for 15 min. 

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