Halcinonide Ointment

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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1 DEFINITION

Halcinonide Ointment is Halcinonide in a suitable ointment base. It contains NLT 90.0% and NMT 110.0% of the labeled amount of halcinonide (C₂₄H₃₂CIFO₅).

2 IDENTIFICATION

A. The retention time of the halcinonide peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the halcinonide peak of the Sample solution corresponds to that of the Diluted standard stock solution, as obtained in the test for Organic Impurities.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Acetonitrile and water (50:50)

Internal standard solution: 6 µg/mL of butylparaben in acetonitrile

Standard stock solution: 0.04 mg/mL of USP Halcinonide RS in Internal standard solution

Standard solution: 0.02 mg/mL of USP Halcinonide RS from Standard stock solution prepared as follows. Mix equal volumes of Mobile phase and Standard stock solution.

Sample solution: Nominally 0.02 mg/mL of halcinonide in Mobile phase prepared as follows. Transfer an equivalent to 1 mg of halcinonide from a quantity of Ointment to a glass-stoppered, 50-mL centrifuge tube, and add 25.0 mL of Internal standard solution and 5.0 mL of hexane. Place in a water bath at 58 ± 2° for 3 min, then mix in a vortex mixer for 1 min until the sample is well dispersed. Repeat the above-specified heating and mixing step once. Cool in an ice-methanol bath for 15 min, or until the two phases separate, centrifuging if necessary. Transfer 5.0 mL of the lower layer to a 15-mL centrifuge tube, and add 5.0 mL of Mobile phase.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for butylparaben and halcinonide are 0.6 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between halcinonide and butylparaben

Relative standard deviation: NMT 3.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of halcinonide (C₂₄H₃₂CIFO₅) in the portion of Ointment taken:

Result = (R_U/R_S) x (C_S/C_U) x 100

R_U = peak response ratio of halcinonide to butylparaben from the Sample solution

R_S = peak response ratio of halcinonide to butylparaben from the Standard solution

C_S = concentration of USP Halcinonide RS in the Standard solution (mg/mL)

C_U = nominal concentration of halcinonide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

MINIMUM FILL (755): Meets the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A: 10 mM ammonium acetate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent 1: Acetonitrile and water (60:30), saturated with hexane

Diluent 2: Acetonitrile and water (10:90)

Standard stock solution: 0.2 mg/mL of USP Halcinonide RS in Diluent 1

Diluted standard stock solution: 0.1 mg/mL of USP Halcinonide RS in Diluent 2 from the Standard stock solution

Standard solution: 0.2 µg/mL each of USP Halcinonide RS in Diluent 2 from the Standard stock solution

Sample stock solution: Nominally 0.2 mg/mL of halcinonide in Diluent 1 prepared as follows. Transfer a portion of Ointment equivalent to 4 mg of halcinonide to a 50-mL centrifuge tube. Add 10 mL of Diluent 1 and 20 mL of hexane heated at 58 ± 2° for 20 min. Shake for NLT 1 min initially to ensure dispersion and at 5-min intervals thereafter. Cool, centrifuge at 3000 rpm for 10 min, and transfer the lower layer to a 20-mL volumetric flask. Repeat the extraction with an additional 5 mL of Diluent 1 and 20 mL of hexane each time. Dilute with Diluent 1 to volume.

Sample solution: 0.1 mg/mL of halcinonide from the Sample stock solution in Diluent 2

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification test B, use a diode array detector in the range of 200-450 nm.

Column: 2.1-mm × 15-cm; 1.8-µm packing L1

Flow rate: 0.3 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Relative standard deviation: NMT 2.4%

Signal-to-noise ratio: NLT 50

Samples: Diluted standard stock solution, Standard solution, and Sample solution

Analysis

[NOTE-The Diluted standard stock solution is used for Identification test B.]

Calculate the percentage of any individual unspecified impurity in the portion of Ointment taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = peak response of halcinonide from the Standard solution

C_S = concentration of USP Halcinonide RS in the Standard solution (µg/mL)

C_U = nominal concentration of halcinonide in the Sample solution (µg/mL)

Acceptance criteria: See Table 2.

Table 2

^a Drug substance process impurity included in the table for identification only.

6 SPECIFIC TESTS

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): Meets the requirements for the absence of Staphylococcus aureus and Pseudomonas aeruginosa

7 ADDITIONAL REQUIREMENTS

7.1 PACKAGING AND STORAGE

Preserve in well-closed containers. Store at room temperature. Avoid excessive heat.

7.2 USP REFERENCE STANDARDS (11)

USP Halcinonide RS