Halcinonide Cream

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Halcinonide Cream is Halcinonide in a suitable cream 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-Vis 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)

Diluent: Acetonitrile and water (2:1), saturated with hexanes. [NOTE-Prepare on the day of use.]

Internal standard solution: 150 µg/mL of Progesterone in hexanes-saturated Diluent

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

Standard solution: 0.02 mg/mL of USP Halcinonide RS in hexanes-saturated Diluent prepared as follows. Transfer 5.0 mL of Standard stock solution to a 50-mL volumetric flask. Add 4.0 mL of Internal standard solution, and dilute with hexanes-saturated Diluent to volume.

Sample solution: Nominally 0.02 mg/mL of halcinonide in hexanes-saturated Diluent prepared as follows. Transfer a quantity of Cream equivalent to 0.5 mg of halcinonide to a glass-stoppered, 50-mL centrifuge tube. Add 12 mL of hexanes-saturated Diluent and 20 mL of hexanes, and shake for 1 min. Place in a heated ultrasonic bath at 58 ± 2° for 20 min, initially shaking for 1-2 min to ensure dispersion, and at 5-min intervals thereafter, on a vibratory mixer. Cool, centrifuge, and transfer the lower layer to a 25-mL volumetric flask. Add 5 mL of hexanes-saturated Diluent to the tube, mix for 1 min, then centrifuge. Transfer the lower layer to the volumetric flask, and repeat the extraction with an additional 5 mL of hexanes-saturated Diluent, combining the extracts in the flask. Add 2.0 mL of Internal standard solution to the flask, dilute with hexanes-saturated Diluent to volume, and mix. If necessary, clarify a portion of the solution by centrifugation.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm x 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

3.3 System suitability

Sample: Standard solution

[NOTE-The relative retention times for halcinonide and progesterone are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.5 between halcinonide and progesterone

Relative standard deviation: NMT 3.0%, peak response ratio of halcinonide to progesterone

3.4 Analysis

Samples: Standard solution and Sample solution

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

Result = (R_U/R_S) x (C_S/C_U) x 100

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

R_S = peak response ratio of halcinonide to progesterone 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 of ammonium acetate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

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

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 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 Cream equivalent to 4 mg of halcinonide to a 50-mL centrifuge tube. Add 10 mL of Diluent 1 and 20 mL of hexanes 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 the 20-mL volumetric flask. Repeat the extraction with an additional 5 mL of Diluent 1 and 20 mL of hexanes each time. Dilute with Diluent 1 to volume.

Sample solution: 0.1 mg/mL of halcinonide from 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 x 15-cm; 1.7-µm packing L1

Flow rate: 0.3 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[NOTE-See Table 2 for 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 Cream taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of each individual 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 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