(sye'' kloe pir' ox).
» Ciclopirox contains not less than 98.0 percent and not more than 101.0 percent of C12H17NO2, calculated on the dried basis.
Packaging and storage Preserve in well-closed containers, protected from light. Store at a temperature between 15 and 30.
USP Reference standards 11
Identification, Infrared Absorption 197K.
Loss on drying 731 Dry it in vacuum to constant weight: it loses not more than 1.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: not more than 0.001%.
Related compounds [noteCarry out the operations avoiding exposure to actinic light. All materials in direct connection with Ciclopirox, like column materials, reagents, solvents, and others should contain only very low amounts of extractable metal cations. ]
Mobile phase Prepare a filtered and degassed mixture of an edetate disodium solution (0.96 in 1000), acetonitrile, and glacial acetic acid (770:230:0.1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Rinsing solution Prepare a mixture of water, acetonitrile, glacial acetic acid, and acetylacetone (500 : 500 : 1:1).
Standard stock solution Dissolve USP Ciclopirox Related Compound A RS and USP Ciclopirox Related Compound B RS, accurately weighed, in an appropriate volume of acetonitrile and Mobile phase solution (approximate ratio, 1:7). Further dilute with Mobile phase to obtain a solution having a known final concentration of about 1.5 mg each per mL.
Standard solution A Dilute 1.0 mL of Standard stock solution to 200.0 mL with a mixture of Mobile phase and acetonitrile (9:1).
Standard solution B Dilute 2.0 mL of Standard solution A to 10.0 mL with a mixture of Mobile phase and acetonitrile (9:1).
Test solution Dissolve 30 mg of Ciclopirox, accurately weighed, in a mixture of 2 mL of acetonitrile and 15 mL of Mobile phase. If necessary, use an ultrasonic bath. Dilute with Mobile phase to 20.0 mL.
Resolution solution Mix 5 mL of Standard stock solution with 5 mL of the Test solution.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a detector capable of recording at both 220 nm and 298 nm and a 4.0-mm × 8-cm column that contains packing L10. [noteCiclopirox related compound A has an intense absorbance at 220 nm, and 6-cyclohexyl-4-methyl-2(1H)-pyridone, ciclopirox related compound B, and ciclopirox have intense absorbances at 298 nm. ] The flow rate is about 0.7 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure at 298 nm: the resolution, R, between the ciclopirox related compound B peak and ciclopirox peak is not less than 2.0. Chromatograph the Standard solution B, and record the peak responses as directed for Procedure at 298 nm: the chromatogram obtained shows at 298 nm a peak corresponding to ciclopirox related compound B with a signal-to-noise ratio of not less than 3. Chromatograph the Test solution, and record the peak responses as directed for Procedure at 298 nm: the tailing factor for the ciclopirox peak is less than 2.0.
Procedure Separately inject equal volumes (about 10 µL) of Standard solution A, Standard solution B, and the Test solution into the chromatograph, and record the chromatograms. [noteIn order to ensure desorption of disruptive metal ions, every new column must be rinsed with the Rinsing solution over a period of not less than 15 hours and then with the Mobile phase for not less than 5 hours with a flow rate of 0.2 mL per minute. The chromatographic run time is not less than 2.5 times the retention time of the ciclopirox peak. ] The relative retention times are about 0.5 for ciclopirox related compound A, 0.9 for 6-cyclohexyl-4-methyl-2(1H)-pyridone, 1.0 for ciclopirox, and 1.3 for ciclopirox related compound B. The peak response at 220 nm of the ciclopirox related compound A peak in the chromatogram obtained from the Test solution is not more than the peak response at 220 nm of the corresponding peak in the chromatogram obtained from Standard solution A (0.5%). The sum of responses at 298 nm of the peaks in the chromatogram obtained from the Test solution is not more than the peak response at 298 nm of the ciclopirox related compound B peak in the chromatogram obtained from Standard solution A (0.5%). At 298 nm disregard any peak due to the solvent and any peak with a response less than the response of the ciclopirox related compound B peak in the chromatogram obtained from Standard solution B at 298 nm (0.1%).
Assay Dissolve 150 mg of Ciclopirox, accurately weighed, in 20 mL of methanol. Add 20 mL of water, mix, and titrate with 0.1 N sodium hydroxide VS, determining the endpoint potentiometrically. Carry out a blank test. Determine the factor of the 0.1 N sodium hydroxide VS using 100 mg of benzoic acid, accurately weighed, and titrate under the conditions prescribed above. Each mL of 0.1 N sodium hydroxide is equivalent to 20.73 mg of C12H17NO2.
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USP35NF30 Page 2659Pharmacopeial Forum: Volume No. 33(4) Page 642