Flunisolide

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₂₄H₃₁FO₆· ½H₂O 443.51

Pregna-1,4-diene-3,20-dione, 6-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-, hemihydrate, (6α,11β,16α)-.

6α-Fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with acetone, hemihydrate CAS RN^®: 77326-96-6; UNII: QK4DYS664X.

Anhydrous 434.51 CAS RN^®: 3385-03-3.

>> Flunisolide contains not less than 97.0 percent and not more than 102.0 percent of C₂₄H₃₁FO₆, calculated on the anhydrous basis.

1 Packaging and storage

Preserve in well-closed containers.

2 USP REFERENCE STANDARDS (11)

USP Flunisolide RS

3 Identification

Change to read:

A:Spectroscopic Identification Tests (197), Infrared Spectroscopy: 197K (CN 1-May-2020).

Change to read:

B:SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 (CN 1-May-2020)-

Solution: 10 µg per mL..

Medium: methanol.

3.1 SPECIFIC ROTATION (781S)

Between +103° and + 111°.

Test solution: 10 mg per mL, in chloroform.

3.2 LOSS ON DRYING (731)

Dry it in vacuum at 60° for 3 hours: it loses not more than 1.0% of its weight.

3.3 WATER DETERMINATION, Method I (921)

The anhydrous form contains not more than 1.0%. The hemihydrate form contains between 1.8% and 2.5% (determined on a dried specimen).

3.4 RESIDUE ON IGNITION (281)

Not more than 0.1% from 250 mg.

4 Chromatographic purity

Standard solutions-Prepare a solution of USP Flunisolide RS in acetone to contain 10 mg per mL (Standard solution A). Dilute 1 mL of Standard solution A with acetone to 100 mL (Standard solution B).

Test preparation-Prepare a solution of Flunisolide in acetone to contain 10 mg per mL.

Procedure-Apply 10-µL volumes of Standard solution A, Standard solution B, and the Test preparation to a suitable thin-layer chromatographic plate (see Chromatography (621)) coated with a 0.25-mm layer of chromatographic silica gel mixture. Place the plate in a suitable chromatographic chamber previously equilibrated with a mixture of toluene and alcohol (90:10), seal the chamber, and develop the chromatogram until the solvent front has moved three-fourths of the length of the plate. Remove the plate, allow the solvent to evaporate, and examine the plate under short-wavelength UV light: the R_F value of the principal spot obtained from the Test preparation corresponds to that obtained from Standard solution A. No secondary spot exhibits an intensity greater than that of the principal spot from Standard solution B.

5 Assay

Mobile phase-Prepare a suitable degassed solution of water and acetonitrile (3:2) such that at an approximate flow rate of 1.6 mL per minute, the retention time of Flunisolide is about 6 minutes.

Standard preparation-Dissolve an accurately weighed quantity of USP Flunisolide RS in Mobile phase to obtain a solution having a known concentration of about 0.2 mg per mL.

Assay preparation-Using 20 mg of Flunisolide, accurately weighed, proceed as directed for Standard preparation.

Chromatographic system (see Chromatography (621))-The liquid chromatograph is equipped with a 254-nm detector and a 4-mm x 25-cm column that contains 5- to 10-µm packing L7. The flow rate is about 1.6 mL per minute. Chromatograph the Standard preparation, and record the peak response as directed for Procedure: the column efficiency is not less than 2700 theoretical plates; the tailing factor for the flunisolide peak is not more than 1.7; and the relative standard deviation for replicate injections is not more than 1.0%.

Procedure-Separately inject equal volumes (between 15 µL and 30 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C₂₄H₃₁FO₆ in the portion of Flunisolide taken by the formula:

(434.51/443.51)100C(r_U/r_S)

in which 434.51 and 443.51 are the molecular weights of C₂₄H₃₁FO₆  and C₂₄H₃₁FO₆· ½H₂O, respectively; C is the concentration, in mg per mL, of USP Flunisolide RS in the Standard preparation; and r_U and r_S are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.