Hydroxyprogesterone Caproate Injection

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

Hydroxyprogesterone Caproate Injection is a sterile solution of Hydroxyprogesterone Caproate in a suitable vegetable oil. It contains NLT 90.0% and NMT 110.0% of the labeled amount of hydroxyprogesterone caproate (C₂₇H₄₀O₄).

2 IDENTIFICATION

2.1 A.

Sample solution: Transfer a volume of Injection, equivalent to 125 mg of hydroxyprogesterone caproate, to a 60-mL separator containing 10 mL of solvent hexane, 8 mL of methanol, and 2 mL of water. Insert the stopper, shake for 2 min, and allow the phases to separate. The lower layer is the Sample solution.

Analysis: To 3 mL of the Sample solution add sulfuric acid dropwise until a color develops, then add 3 mL of methanol.

Acceptance criteria: A purple color develops and the solution, when viewed under long-wavelength UV light, exhibits a pale yellow fluorescence.

2.2 B.

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

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol and water (80:20)

Standard solution: 0.05 mg/mL of USP Hydroxyprogesterone Caproate RS in methanol

Sample solution: Nominally 0.05 mg/mL of hydroxyprogesterone caproate from an appropriate volume of Injection in methanol

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 242 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 20 µL

Run time: Twice the retention time of hydroxyprogesterone caproate

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 4000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyprogesterone caproate (C₂₇H₄₀O₄) in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 ORGANIC IMPURITIES

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.5 µg/mL of USP Hydroxyprogesterone Caproate RS in methanol

Sample stock solution: Transfer 2.0 mL of Injection, equivalent to 500 mg of hydroxyprogesterone caproate, to a 100-mL volumetric flask and dilute with methanol to volume.

Sample solution: Nominally 0.25 mg/mL of hydroxyprogesterone caproate prepared as follows. Transfer an appropriate amount of Sample stock solution to a suitable volumetric flask and dilute with methanol to volume.

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Signal-to-noise ratio: NLT 10

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hydroxyprogesterone or any individual unspecified degradation product in the portion of Injection taken:

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

r_U = peak response of each corresponding degradation product from the Sample solution

r_S = peak response of hydroxyprogesterone caproate from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. Disregard any peak less than 0.05%.

Table 1

ᵃ 17-Hydroxypregn-4-ene-3,20-dione.

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method 1: NMT 0.2%

OTHER REQUIREMENTS: Meets the requirements in Injections and Implanted Drug Products (1).

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-dose or in multiple-dose containers, preferably of Type I or Type III glass. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Hydroxyprogesterone Caproate RS