Alprostadil Injection

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

Alprostadil Injection is a sterile solution of Alprostadil in Dehydrated Alcohol. It contains NLT 90.0% and NMT 115.0% of the labeled amount of alprostadil (C20H340).

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

Sample: Dry an amount of Injection, equivalent to 2 mg of alprostadil, on 500 mg of spectroscopic grade potassium bromide at 40°-50° under vacuum. Prepare a pellet from this mixture.

Standard: A solution of USP Alprostadil RS dissolved in dehydrated alcohol and processed as described in the Sample

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Solution A: 40 mg/mL of a-bromo-2'-acetonaphthone in acetonitrile, freshly prepared

Solution B: 5 mg/mL of diisopropylethylamine in acetonitrile, freshly prepared

Mobile phase: Methylene chloride, 1,3-butanediol, and water (1000:6:0.5)

Internal standard solution: 50 µg/mL of ethylparaben in methylene chloride

Standard stock solution: 0.5 mg/mL of USP Alprostadil RS in dehydrated alcohol

Standard solution: 0.13 mg/mL of USP Alprostadil RS, prepared as follows. Gently evaporate a 0.5-mL portion of the Standard stock solution to dryness with a stream of nitrogen. Add 150 µL of Solution A, rinse the inside of the container with this solution, and swirl. Add 150 µL of Solution B to the container, rinse the inside of the container with this solution, and swirl. Cap and sonicate to dissolve. Heat the container at 45° for 45 min, swirling occasionally. Sonicate again after heating is complete. Discard the specimen if the entire sample does not dissolve. Evaporate the solution using a stream of nitrogen, add 2.0 mL of Internal standard solution, and sonicate to dissolve. Discard the specimen if the entire sample does not dissolve.

Sample solution: Nominally 0.13 mg/mL of alprostadil, prepared as follows. Pool the contents of several containers of the Injection. Gently evaporate a volume, equivalent to 0.25 mg of alprostadil, to dryness using a stream of nitrogen. Proceed as directed for the Standard solution, beginning with "Add 150 µL of Solution A".

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.4-mm x 25-cm; packing L18

Flow rate: 1.5 mL/min

Injection volume: Equal volumes of Standard solution and Sample solution

3.3 System suitability

Sample: Standard solution

[NOTE-The relative retention times for ethylparaben and alprostadil are about 0.4 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 9.0 between alprostadil and the internal standard

Relative standard deviation: NMT 2.5%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of alprostadil (C20H34O5) in the portion of Injection taken:

Result = (R_U/R_S) x (C_S/C_U) x 100

R_U = peak response ratio of alprostadil to the internal standard from the Sample solution

R_S = peak response ratio of alprostadil to the internal standard from the Standard solution

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

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

Acceptance criteria: 90.0%-115.0%

4 SPECIFIC TESTS

4.1 BACTERIAL ENDOTOXINS TEST (85)

It contains NMT 5 USP Endotoxin Units/100 µg of alprostadil.

4.2 STERILITY TESTS (71)

It meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration.

4.3 WATER DETERMINATION, Method (921)

NMT 0.4%

4.4 OTHER REQUIREMENTS

It meets the requirements in Injections and Implanted Drug Products (1).

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, single-dose containers, preferably of Type I glass. Store in a refrigerator.

USP REFERENCE STANDARDS (11)

USP Alprostadil RS