Echothiophate Iodide for Ophthalmic Solution
» Echothiophate Iodide for Ophthalmic Solution is sterile Echothiophate Iodide. It may contain Mannitol or other suitable diluent. It contains not less than 95.0 percent and not more than 115.0 percent of the labeled amount of C9H23INO3PS.
Packaging and storage Preserve in tight containers, preferably of Type I glass, at controlled room temperature.
Completeness of solution 641 The contents of 1 container dissolve in 10 mL of carbon dioxide-free water to yield a clear solution.
A: Dissolve a quantity, equivalent to about 12 mg of echothiophate iodide, in 10 mL of water. To 1 mL of this solution add 0.2 mL of 2 N hydrochloric acid and 0.2 mL of 30 percent hydrogen peroxide: the color turns brown. Add a few drops of solvent hexane, and shake: the solvent hexane acquires a pink color.
B: To 5 mL of the solution prepared for Identification test A add 0.5 mL of sodium hydroxide solution (1 in 2), heat at 50 for 2 minutes, cool to room temperature, then add 1 mL of sodium nitroferricyanide TS: a deep-red color is produced.
Sterility 71: meets the requirements.
Water [noteDry all glassware used in the following procedure at 105 for 4 hours, and store in a desiccator or dry box. Perform as many operations as possible in a dry box. ]
Dry alcohol Wash about 150 g of 8- to 12-mesh type 3A molecular sieve with several portions of dehydrated alcohol to remove the fine particles. Place the washed molecular sieve in a shallow borosilicate glass tray, heat in an oven at 350 for 2 hours, and cool in a dry box. Transfer the dry molecular sieve to a 1-liter conical flask, add about 700 mL of dehydrated alcohol, insert the stopper, mix, and allow to stand for not less than 48 hours before using.
Internal standard solution [notePrepare this solution fresh daily. ] Place 0.17 mL of methanol in a 100-mL volumetric flask, add Dry alcohol to volume, and mix.
Standard preparations [notePrepare these solutions fresh daily. ] Into three 25-mL volumetric flasks, each containing about 15 mL of Internal standard solution, transfer 5 µL, 40 µL, and 75 µL of water, respectively. Dilute with Internal standard solution to volume, and mix.
Test preparation Carefully remove the protective retainer and cap from 5 vials of Echothiophate Iodide for Ophthalmic Solution without removing the elastomeric septum closure. Discard the separated parts, and weigh accurately each closed vial and contents. Inject through the septum of each vial 400 µL of Internal standard solution, accurately measured, using a suitable gas-tight syringe, and allow to stand for 1 hour, swirling occasionally to dissolve the residue. After 1 hour, using a gas-tight syringe, remove 300 µL of solution from each vial, transfer to a dry small-volume sample-collecting vial equipped with a sampling valve system,* and mix the combined solutions.
Chromatographic system (see Chromatography 621)The chromatograph is equipped with a thermal conductivity detector and a 2-mm × 1.8-m silylated glass column packed with 80- to 100-mesh surface-silanized packing S3. The column is maintained at a temperature of about 115, the injection port and detector block are maintained at temperatures of about 200 and 225, respectively, and dry helium is used as the carrier gas at a flow rate of about 45 mL per minute. Chromatograph a sufficient number of injections of a Standard preparation, and record the peak responses as directed for Procedure: the resolution factor between the water and methanol peaks is not less than 2.0; and the relative standard deviation is not more than 5.0%.
Procedure Inject a portion (3 µL to 4 µL) of each Standard preparation into the chromatograph, record the chromatogram, and measure the responses for the first (water) and second (methanol) major peaks obtained for each. Plot the ratios of the peak responses of water to methanol versus the concentration, in mg per mL, of water in each Standard preparation. [noteIf the plot is not linear, discard it, and repeat the chromatography on additional portions of the Standard preparations. ] Similarly inject a portion of the Test preparation, record the chromatogram, and measure the responses for the two major peaks. By comparison with the linear standard plot, determine the concentration, in mg per mL, of water in the Test preparation as that corresponding to the ratio of the peak responses of water to methanol from the Test preparation. Remove the elastomeric septum closure from each test vial, discard the contents, and rinse each vial and closure with several portions of methanol. Dry the vials and the closures in a stream of dry nitrogen, weigh accurately, and subtract this weight from that of the closed vials and contents obtained as directed under Test preparation. Calculate the water content, in percentage, taken by the formula:
100CV / Win which C is the concentration, in mg per mL, of water in the Test preparation, V is the volume, in mL, of Internal standard solution added to each test specimen vial as directed under Test preparation, and W is the average weight, in mg, of the test specimens in the vials: not more than 2.0% is found.
Assay [noteIn the preparation of all reagents, and throughout this procedure, wherever water is specified, use only water that has been distilled, boiled for 10 minutes, and cooled while protected from the atmosphere. ] Dissolve the contents of a counted number of vials of Echothiophate Iodide for Ophthalmic Solution, equivalent to not less than 30 mg of echothiophate iodide, by adding 5.0 mL of water to each vial. Combine the solutions, and mix. Dilute a portion of the mixture, equivalent to about 12 mg of echothiophate iodide, with water to 40 mL, and proceed as directed for Procedure in the Assay under Echothiophate Iodide, beginning with Add 10.0 mL of pH 12 phosphate buffer.
* Suitable sample-collecting vials and sampling valve systems are available as catalog Nos. 13098 and 13099 3-mL and 5-mL vials, and catalog No. 10135 valve, from Pierce Chemical Co., Box 117, Rockford, IL 61105.
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