C26H28Cl2N4O4 531.43

Piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis-.
(±)-cis-1-Acetyl-4-[p-[[2-(2,4-dichlorophenyl)-2-(imidazol-1- ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine [65277-42-1].

Packaging and storage— Preserve in well-closed containers.

USP Reference standards 11— USP Ketoconazole RS.

Identification, Infrared Absorption 197K.

Melting range 741: between 148 and 152.

Specific rotation 781S: between 1 and +1 (t = 20).

Loss on drying 731— Dry it in vacuum at 80 for 4 hours: it loses not more than 0.5% of its weight.

Residue on ignition 281: not more than 0.1% from 2 g.

Heavy metals, Method II 231: 0.002%.

Chromatographic purity— Dissolve 30 mg in 3.0 mL of chloroform (Test solution). Dissolve a suitable quantity of USP Ketoconazole RS in chloroform to obtain a Standard solution having a known concentration of 10 mg per mL. Dilute a portion of this solution quantitatively with chloroform to obtain a Diluted standard solution having a concentration of 1.0 mg per mL. Apply separate 10-µL portions of the Test solution and the Standard solution and a 2-µL portion of the Diluted standard solution to the starting line of a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in a suitable unsaturated chamber with a solvent system consisting of a mixture of n-hexane, ethyl acetate, methanol, water, and glacial acetic acid (42:40:15:2:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, and air-dry. Expose the plate to iodine vapors in a closed chamber, and locate the spots: the principal spot obtained from the Test solution has about the same size and RF value as that obtained from the Standard solution, and the sum of the intensities of any secondary spots obtained from the Test solution does not exceed the intensity of the principal spot obtained from the Diluted standard solution.

Organic volatile impurities, Method IV 467: meets the requirements.

Residual solvents 467: meets the requirements.

Assay— Dissolve about 200 mg of Ketoconazole, accurately weighed, in 40 mL of glacial acetic acid. Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 26.57 mg of C26H28Cl2N4O4.

Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials

USP29–NF24 Page 1216

Phone Number : 1-301-816-8394