A: Infrared Absorption 197M.

B: 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.

Test solution: 0.5% (w/v) of Fluticasone Propionate in dichloromethane (0.5 g in 100 mL).

Solution A— Mix 0.5 mL of phosphoric acid in 1000 mL of acetonitrile.

Solution B— Mix 0.5 mL of phosphoric acid in 1000 mL of methanol.

Solution C— Mix 0.5 mL of phosphoric acid in 1000 mL of water.

Mobile phase— Use variable mixtures of Solution A, Solution B, and Solution C, as directed under Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Transfer approximately 2.0 mg of USP Fluticasone Propionate System Suitability Mixture RS to 5 mL of Solution A, and sonicate to dissolve. Add 5 mL of Solution C, and mix.

Test solution— Transfer approximately 2.0 mg of Fluticasone Propionate to 5 mL of Solution A, and sonicate to dissolve. Add 5 mL of Solution C, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 239-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 40. The chromatograph is programmed (see Table 1), as follows. Chromatograph the System suitability solution, and measure the peak responses as directed for Procedure: the resolution, R, between fluticasone propionate related compound B and fluticasone propionate related compound C is not less than 0.6; the resolution, R, between fluticasone propionate related compound D and fluticasone propionate is not less than 1.5; the relative retention times and limits are as provided in Table 2.

Procedure— Separately inject a volume (about 50 µL) of the System suitability solution and the Test solution into the chromatograph, record the chromatograms, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Fluticasone Propionate taken by the formula: in which ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks.

Standard stock solution— Transfer about 20 µL of bromofluoromethane to 10 mL of dimethylformamide, and mix. Dilute 10 µL of this solution with 1 mL of dimethylformamide (0.002% v/v).

Standard solution— Dilute 10 µL of Standard stock solution with 1 mL of dimethylformamide, and mix (0.00002% v/v).

Test solution— Dissolve 200 mg of Fluticasone Propionate in 1.0 mL of dimethylformamide.

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with an electron-capture detector, a 0.32-mm × 25-m capillary column coated with a 5-µm film of phase G27 and a split injection system. The carrier gas is nitrogen, flowing at a rate of about 2.8 mL per minute. The make-up gas is nitrogen, flowing at a rate of 30 mL per minute. The column temperature is programmed as follows. Initially the temperature of the column is equilibrated at 40 for 3.5 minutes, then the temperature is increased at the rate of 30 per minute to 200, and maintained at 200 for 10 minutes. The split injector (70:1) is maintained at a temperature of 85, and the detector temperature is maintained at 250. Chromatograph the Standard solution, and record the peak responses as directed for Procedure.

Procedure— Separately inject equal volumes (about 5 µL) of the Standard solution and the Test solution into the chromatograph, and measure the responses for the bromofluoromethane peaks. The intensity of bromofluoromethane peak in the chromatogram of the Test solution is less than the intensity of bromofluoromethane peak in the chromatogram of the Standard solution.

Internal standard solution— Prepare a 0.05% (v/v) solution of tetrahydrofuran in dimethylformamide.

Standard solution— Prepare 0.05% (v/v) of acetone in Internal standard solution.

Test solution— Dissolve an accurately weighed quantity of Fluticasone Propionate in Internal standard solution to obtain a solution having a known concentration of about 50 mg per mL.

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector and a 0.53-mm × 25-m column coated with a 2-µm film of phase G15. The carrier gas is nitrogen or helium, flowing at a rate of about 5.5 mL per minute. The column temperature is programmed as follows. Initially the temperature of the column is equilibrated at 60 for 3.5 minutes, then the temperature is increased at the rate of 30 per minute to 180, and maintained at 180 for 3 minutes. The splitless injector temperature is maintained at 150, and the detector temperature is maintained at 250. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0%.

Procedure— Separately inject equal volumes (about 0.1 µL) of the Standard solution and the Test solution into the chromatograph, and record the peak responses. Calculate the percentage of acetone (% w/w) in the portion of Fluticasone Propionate taken by the formula: in which D is the density of acetone at 20; C is the concentration, in g per mL, of Fluticasone Propionate in the Test solution; and RU and RS are the ratios of the acetone peak response to the tetrahydrofuran peak response obtained from the Test solution and the Standard solution, respectively: not more than 1.0% (w/w) is found.

(Official January 1, 2007)

0.01 M Monobasic ammonium phosphate buffer, pH 3.5— Dissolve 11.5 g of monobasic ammonium phosphate in 1000 mL of water, adjust with phosphoric acid to a pH of 3.5 ±0.05, and mix.

Mobile phase— Prepare a filtered and degassed mixture of methanol, 0.01 M Monobasic ammonium phosphate buffer, pH 3.5, and acetonitrile (50:35:15). Make adjustments if necessary (see System Suitability under Chromatography 621).

Resolution solution— Dissolve approximately 2.0 mg of USP Fluticasone Propionate Resolution Mixture RS in 50 mL of Mobile phase.

Standard preparation— Dissolve an accurately weighed quantity of USP Fluticasone Propionate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.04 mg per mL.

Assay preparation— Dissolve an accurately weighed quantity of Fluticasone Propionate in Mobile phase, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a concentration of about 0.04 mg per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 239-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 40. Chromatograph the Resolution solution and the Standard preparation, and record the peak areas as directed for Procedure: the relative retention times are about 1.10 for fluticasone propionate related compound D and 1.0 for fluticasone propionate; the resolution, R, between fluticasone propionate and fluticasone propionate related compound D is not less than 1.5; and the relative standard deviation for replicate injections is not more than 2%.

Procedure— Separately inject equal volumes (about 20 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, in mg, of C25H31F3O5S in the portion of Fluticasone Propionate taken by the formula: in which C is the concentration of USP Fluticasone Propionate RS, in mg per mL, in the Standard preparation; V is the volume, in mL, of the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.