Calcipotriene Cream

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

Calcipotriene Cream contains NLT 90.0% and NMT 110.0% of the labeled amount of calcipotriene (C₂₇H₄₀O₃)

2 IDENTIFICATION

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

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the

Assay

3 ASSAY

Procedure 

Protect solutions containing calcipotriene from light and air. Prepare the solutions containing calcipotriene NMT 1 h before use. Solution A: 0.132 g/mL of monobasic ammonium phosphate in water

Mobile phase: Methanol and water (70:30)

Diluent: Methanol, Solution A, and water (70: 0.3: 29.7)

Standard stock solution: 0.1 mg/mL of USP Calcipotriene RS in Diluent. Sonicate if necessary.

Standard solution: 2.0 µg/mL of USP Calcipotriene RS prepared as follows. Transfer 5 mL of Standard stock solution into a 250-mL volumetric flask, add 50 mL of tetrahydrofuran, and dilute with Diluent to volume.

Sample stock solution: Nominally equivalent to 0.01 mg/mL of calcipotriene in tetrahydrofuran prepared as follows. Transfer Cream nominally equivalent to 0.25 mg of calcipotriene to a 25-mL volumetric flask. Add 10 mL of tetrahydrofuran and sonicate for 20 min with intermittent shaking. Cool to room temperature and dilute with tetrahydrofuran to volume.

Sample solution: Nominally equivalent to 2.0 µg/mL of calcipotriene prepared as follows. Transfer 5 mL of Sample stock solution into a suitable container. Add 20 mL of Diluent, mix, and sonicate for 15 min. Pass through a Teon filter of 0.45-µm pore size and discard the first few milliliters of the filtrate.

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 264 nm. For Identification B, use a diode array detector in the range of 190–400 nm.

Column: 4.6-mm × 15-cm; 3-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 50 µL

System suitability 

Sample: Standard solution

Suitability requirements 

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of calcipotriene (C₂₇H₄₀O₃) in the portion of Cream taken:

Result = (r_U/r_S) x (C_S/C_U) × 100 

r_U = peak response of calcipotriene from the Sample solution

r_S = peak response of calcipotriene from the Standard solution

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

C_U = nominal concentration of calcipotriene 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

Protect solutions containing calcipotriene from light and air. Prepare the Standard solution and the Sample solution NMT 1 h before use. Prepare the System suitability solution daily.

Mobile phase: See Table 1.

Diluent: Prepare as directed in the Assay.

System suitability stock solution: 0.125 mg/mL of USP Calcipotriene RS and 2.0 µg/mL of USP Calcipotriene Related Compound C RS in Diluent

System suitability solution: 0.0125 mg/mL of USP Calcipotriene RS and 0.2 µg/mL of USP Calcipotriene Related Compound C RS prepared as follows. Transfer 1 mL of System suitability stock solution to a 10-mL volumetric flask. Add 1 mL of tetrahydrofuran and dilute with Diluent to volume.

Standard stock solution: 62.5 µg/mL of USP Calcipotriene RS prepared as follows. Transfer an appropriate amount of USP Calcipotriene RS to a suitable volumetric flask, add Diluent equivalent to 50% of the nal volume, and sonicate to dissolve. Further add tetrahydrofuran equivalent to 25% of the nal volume and dilute with Diluent to volume.

Standard solution: 0.125 µg/mL of USP Calcipotriene RS in Diluent, from Standard stock solution

Sensitivity solution: 0.0125 µg/mL of USP Calcipotriene RS in Diluent, from Standard solution

Sample solution: Nominally 0.0125 mg/mL of calcipotriene prepared as follows. Transfer Cream equivalent to 0.25 mg of calcipotriene to a 20-mL volumetric flask and add 5 mL of tetrahydrofuran. Sonicate for 15 min with intermittent shaking. Cool to room temperature and dilute with Diluent to volume. Place the volumetric flask in a beaker containing ice-cold water for 2–3 min, and pass the solution through a 0.45- μm Teon filter. Discard the first few milliliters of the filtrate.

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 264 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 100 µL

System suitability 

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements 

Resolution: NLT 1.2 between calcipotriene related compound C and calcipotriene, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis 

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Cream taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) × 100 

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

r_S = peak response of calcipotriene from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

^a(5Z,7E,22E,24R)-24-Cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1α,3β,24-triol.

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 102 cfu/g. The total yeasts and molds count is NMT 101 cfu/g. It meets the requirements of the tests for the absence of Staphylococcus aureus and Pseudomonas aeruginosa species.

pH 〈791〉

Sample solution: 10 g of Cream in 100 mL of water

Acceptance criteria: 7.0–8.5

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature. Do not freeze.

USP Reference Standards 〈11〉

USP Calcipotriene RS

USP Calcipotriene Related Compound C RS

(5E,7E,22E,24S)-24-Cyclopropyl-9,10-secochola-5,7,10(19),22-tetraene-1α,3β,24-triol.

C₂₇H₄₀O₃ 412.6  (USP 1-Dec-2021)