Indomethacin for Injection
» Indomethacin for Injection contains an amount of Indomethacin Sodium equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of indomethacin (C19H16ClNO4).
Packaging and storage Preserve in Containers for Sterile Solids as described under Injections 1.
USP Reference standards 11
USP Endotoxin RS
Constituted solution At the time of use, it meets the requirements for Constituted Solutions under Injections 1.
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B: Thin-Layer Chromatographic Identification Test 201
Test solution Dissolve Indomethacin for Injection in methanol to obtain a solution having a concentration of about 5 mg of indomethacin per mL.
Standard solution: 5 mg per mL in methanol.
Developing solvent system: a mixture of chloroform and glacial acetic acid (19:1).
Procedure Proceed as directed in the chapter, except to dry the spots with the aid of a current of air. The intensity and RF value of the principal spot obtained from the Test solution correspond to those obtained from the Standard solution.
Bacterial endotoxins Using a test solution, prepared by dissolving Indomethacin for Injection in LAL Reagent Water to obtain a concentration of 1.0 mg of indomethacin per mL, proceed as directed under Bacterial Endotoxins Test 85. It contains not more than 20.0 USP Endotoxin Units per mg of indomethacin.
pH 791: between 5.0 and 7.0, in a solution in water (1 in 2000) containing 0.3 mL of saturated potassium chloride solution per 100 mL.
Particulate matter 788: meets the requirements for small-volume injections.
Limit of 4-chlorobenzoic acid
Mobile phase and Solvent mixturePrepare as directed in the Assay.
Standard preparation Dissolve a suitable quantity of 4-chlorobenzoic acid, accurately weighed, in acetonitrile to obtain a solution having a known concentration of about 0.22 mg per mL. Transfer 1.0 mL of this solution to a 500-mL volumetric flask, add 150 mL of acetonitrile, dilute with water to volume, and mix. This solution contains about 0.44 µg of 4-chlorobenzoic acid per mL.
Test preparation Use the Assay preparation.
Chromatographic system Prepare as directed in the Assay. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, for the 4-chlorobenzoic acid peak is not less than 1.0.
Procedure Separately inject equal volumes (about 50 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the 4-chlorobenzoic acid peak areas. Calculate the percentage of 4-chlorobenzoic acid in the portion of Indomethacin for Injection taken by the formula:
10(C4 / NCA)(rU / rS)in which C4 is the concentration, in µg per mL, of 4-chlorobenzoic acid in the Standard preparation; N is the number of containers of Indomethacin for Injection taken; CA is the quantity, in mg, of indomethacin (C19H16ClNO4) in each container of Indomethacin for Injection taken, determined as directed herein; and rU and rS are the 4-chlorobenzoic acid peak areas obtained from the Test preparation and the Standard preparation, respectively: not more than 2.2%, equivalent to not more than 5.0%, calculated as indomethacin, is found.
Other requirements It meets the requirements under Sterility Tests 71, Uniformity of Dosage Units 905, and for Labeling under Injections 1.
Mobile phase Prepare a suitable mixture of methanol, water, and phosphoric acid (600:400:1), and pass through a suitable filter having a 0.5-µm or finer porosity. Make adjustments if necessary (see System Suitability under Chromatography 621).
Solvent mixture Prepare a mixture of water, acetonitrile, and phosphoric acid (700:300:1).
Standard preparation Transfer about 20 mg of USP Indomethacin RS, accurately weighed, to a 200-mL volumetric flask, and dissolve in 60 mL of acetonitrile. Dilute with water to volume, and mix.
Assay preparation Select an accurately counted number of containers of Indomethacin for Injection, equivalent to a total of about 10 mg of indomethacin, and constitute each with a volume of Solvent mixture sufficient to obtain solutions containing the equivalent of about 0.5 mg of indomethacin per mL. Wash the contents of these containers with the aid of the Solvent mixture into a 100-mL volumetric flask. Dilute with Solvent mixture to volume, mix, and pass through a filter having a 0.5-µm or finer porosity. Use the filtrate as the Assay preparation.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency determined from the indomethacin peak is not less than 1500 theoretical plates; the capacity factor, k¢, for the indomethacin peak is not less than 3.5; the tailing factor for the indomethacin peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, CA, in mg, of indomethacin (C19H16ClNO4) in each container of Indomethacin for Injection taken by the formula:
100(C/N)(rU / rS)in which C is the concentration, in mg per mL, of USP Indomethacin RS in the Standard preparation; N is the number of containers of Indomethacin for Injection taken; and rU and rS are the indomethacin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3503