Misoprostol

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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C₂₂H₃₈O₅              382.53

Prost-13-en-1-oic acid, 11,16-dihydroxy-16-methyl-9-oxo-, methyl ester, (1R*,2R*,3R*,E)-;

(±)-Methyl (1R,2R,3R)-3-hydroxy-2-[(E)-(4RS)-4-hydroxy-4-methyl-1-octenyl]-5-oxocyclopentaneheptanoate

CAS RN: 59122-46-2; UNII: 0E43V0BB57.

1 DEFINITION

Misoprostol contains NLT 97.0% and NMT 102.0% of C₂₂H₃₈O₅, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 1975 _{(CN 1-MAY-2020)}

Sample solution: 30 mg/mL

Medium: Chloroform

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

PROCEDURE

Mobile phase: 2,2,4-Trimethylpentane, dioxane, and acetonitrile (78:21.5:0.5)

Standard solution: 5.0 mg/mL of USP Misoprostol RS in Mobile phase

Sample solution: 5.0 mg/mL of Misoprostol in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L3

Flow rate: 2 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution

[NOTE-Identify the impurities based on the retention times shown in Impurity Table 1.]

Suitability requirements

Resolution: NLT 1.2, between the second diastereomer peak for 12-epimisoprostol and the Misoprostol peak

Relative standard deviation: NMT 1.0%, for three replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₂H₃₈O₅, in the portion of Misoprostol taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of the Sample solution

r_s = peak response of the Standard solution

C_s = concentration of the Standard solution (mg/mL)

C_u = concentration of the Sample solution (mg/mL)

Acceptance criteria: 97.0%–102.0% on the anhydrous basis

4 IMPURITIES

ORGANIC IMPURITIES

4.1 PROCEDURE 1

Mobile phase, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Record the chromatogram for at least 3 times the retention time of the Misoprostol peak, and measure the peak responses. Identify the impurities based on the retention times shown in Impurity Table 1.

Calculate the percentage of each impurity in the portion of Misoprostol taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of the Standard solution

C_s = concentration of USP Misoprostol RS in the Standard solution (mg/mL)

C_u = concentration of Misoprostol in the Sample solution (mg/mL)

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 1.5%

Impurity Table 1

^a Methyl 7-{(1R*,2S*)-2-[(E)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopent-3-enyl}heptanoate.

^b (E)-Methyl 7-[2-(4-hydroxy-4-methyloct-1-enyl)-5-oxocyclopent-1-enyl]heptanoate.

^c Methyl 7-(3-hydroxy-5-oxocyclopent-1-enyl)heptanoate.

^d Methyl (1S*,2R*,3R*)-3-hydroxy-2-[(E)-4-hydroxy-4-methyl-1-octenyl]-5-oxocyclopentaneheptanoate.

^e Methyl (1S*,2R*,3S*)-3-hydroxy-2-[(E)-4-hydroxy-4-methyl-1-octenyl]-5-oxocyclopentaneheptanoate.

^f 12-Epimisoprostol consists of two diastereomers that are separated under these conditions; integrate both peaks together for the impurity calculations.

4.2 Procedure 2: Content of Diastereomers

Mobile phase: Hexane, Ethanol, and isopropyl alcohol (94:4:2)

Sample solution: 1.0 mg/mL of Misoprostol in Mobile phase

Chromatographic system

(See Chromatography 〈621〉,

Detector: UV 205 nm

Column: 4.6-mm × 25-cm; 5-µm packing L3

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: Sample solution

[Note—Identify the components based on their relative retention times which are about 0.92 for the rst diastereomer peak and 1.0 for the

second diastereomer peak.]

Suitability requirements

Resolution: NLT 2.0, between the two diastereomer peaks

Relative standard deviation: NMT 2.0% from the area of the rst diastereomer peak

Analysis

Sample: Sample solution

Calculate the fraction of the rst diastereomer in the portion of Misoprostol taken:

Result = r₁ /(r₁ + r₂ )

r₁ = peak response for the rst diastereomer

r₂ = peak response for the second diastereomer

Acceptance criteria

Fraction of the rst diastereomer: 0.51–0.56

5 SPECIFIC TESTS

Water Determination, Method Ic〈921〉: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store in a freezer.

USP Reference Standards 〈11〉

USP Misoprostol RS