Printed on: Thu Feb 09 2023, 12:35:11 AM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-91713D53-1941-449A-ADEF-9D15FE2CCBB2_1_en-US

Printed by: Dang Van Vu Official Date: Official as of 01-May-2015 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: j27hd DOI: https://doi.org/10.31003/USPNF_M54303_01_01
1

Detector: UV 205 nm
Misoprostol Dispersion Column: 4.6-mm × 15-cm; 5-µm packing L7
DEFINITION Temperatures
Misoprostol Dispersion is a mixture of Misoprostol and Column: 50 ± 2°; the Mobile phase must be preheated
Hypromellose. It contains NLT 95.0% and NMT 104.0% of prior to introduction on the column.
the labeled amount of misoprostol (C22H38O5). Autosampler: 5 ± 3°
Flow rate: 1.5 mL/min
IDENTIFICATION Injection volume: 100 µL
• A. ULTRAVIOLET ABSORPTION System suitability
Perform both Procedure 1 and Procedure 2. Sample: Standard solution
Procedure 1 [NOTE—USP Misoprostol RS contains 12-epimisoprostol
Medium: Methanol and water (4:1) as a minor component. The relative retention times for
Sample solution: Nominally 16 µg/mL of misoprostol in 12-epimisoprostol and misoprostol are 0.84 and 1.0,
Medium prepared as follows. Dissolve the amount of respectively.]
Misoprostol Dispersion, equivalent to 400 µg of Suitability requirements
misoprostol, in 25 mL of Medium. Resolution: NLT 2.7 between 12-epimisoprostol and
Blank: Prepare a solution of hypromellose in Medium misoprostol
having the same concentration as in the Sample solution. Relative standard deviation: NMT 1.0%
Analysis: Determine UV absorption spectrum of Sample Analysis
solution against the Blank from 330–230 nm. Samples: Standard solution and Sample solution
Acceptance criteria 1: It exhibits no maximum near Calculate the percentage of the labeled amount of
280 nm. misoprostol (C22H38O5) in the portion of Misoprostol

al
Procedure 2 Dispersion taken:
Medium: Methanol and 1 N potassium hydroxide (4:1)
Sample solution: Add 10 mL of Medium to 10 mL of the Result = (rU/rS) × (CS/CU) × 100
Sample solution prepared from Procedure 1. Allow to stand
for 30 min at room temperature. rU = peak response from the Sample solution
Blank: Add 10 mL of Medium to 10 mL of the Blank rS = peak response from the Standard solution
prepared from Procedure 1. Allow to stand for 30 min at
room temperature.
Analysis: Determine UV absorption spectrum of Sample
ci CS

CU
= concentration of USP Misoprostol RS in the
Standard solution (mg/mL)
= nominal concentration of misoprostol in the
solution against the Blank from 330–230 nm. Sample solution (mg/mL)
Acceptance criteria 2: It exhibits a maximum near
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280 nm. Acceptance criteria: 95.0%–104.0%
• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as IMPURITIES
obtained in the Assay. • ORGANIC IMPURITIES
[NOTE—During the addition of water to a solution of
ASSAY misoprostol in isopropyl alcohol, an exothermic
O

• PROCEDURE reaction takes place. After each addition of water,

[NOTE—During addition of water to a solution of invert the flask to mix isopropyl alcohol and water.
misoprostol in isopropyl alcohol, an exothermic Allow the solution to cool to room temperature
reaction takes place. After each addition of water, before the final dilution.]
invert the flask to mix isopropyl alcohol and water. Buffer, Mobile phase, Standard solution, Sample
Allow the solution to cool to room temperature solution, and Chromatographic system: Proceed as
before the final dilution.] directed in the Assay.
Buffer: 1.36 g/L of monobasic potassium phosphate in Diluent: Isopropyl alcohol and water (27:73)
water, adjusted with phosphoric acid to a pH of 3.0 ± 0.1 Blank: Prepare a solution of hypromellose in the Diluent
Mobile phase: Isopropyl alcohol and Buffer (27:73) having the same concentration as in the Sample solution.
Standard stock solution: 0.5 mg/mL of USP Misoprostol RS Diluted standard solution: 0.5 µg/mL of USP
in isopropyl alcohol. [NOTE—This solution is stable up to Misoprostol RS in Diluent from Standard solution
28 days when stored at 5 ± 3°.] Sensitivity solution: 0.1 µg/mL of USP Misoprostol RS in
Standard solution: 0.1 mg/mL of USP Misoprostol RS in Diluent from Diluted standard solution
water from Standard stock solution. [NOTE—This solution is System suitability
stable up to 7 days when stored at 5 ± 3°.] Samples: Standard solution and Sensitivity solution
Sample solution: Nominally 0.1 mg/mL of misoprostol Suitability requirements
prepared as follows. Place an amount of Misoprostol Resolution: NLT 2.7 between 12-epimisoprostol and
Dispersion, equivalent to about 10 mg of misoprostol, misoprostol, Standard solution
into a 100-mL volumetric flask, and add 25 mL of isopropyl Signal-to-noise ratio: NLT 10, Sensitivity solution
alcohol. Shake to disperse the solid, place the solution in an Analysis
ice bath, swirl, and allow to cool for 10 min. Carefully add Samples: Sample solution, Blank, and Diluted standard
about 70 mL of water, previously chilled in a refrigerator, solution
remove from the ice bath, and shake. Sonicate as necessary Calculate the percentage of any individual impurity in the
at a temperature not exceeding 20°. Equilibrate to room portion of Misoprostol Dispersion taken:
temperature, dilute with water to volume, and immediately
cool the solution to 5°. [NOTE—This solution is stable up to Result = (rU/rS) × (CS/CU) × (1/F) × 100
7 days when stored at 5 ± 3°.]
Chromatographic system rU = peak response of any individual impurity from the
(See Chromatography á621ñ, System Suitability.) Sample solution
Mode: LC

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Printed on: Thu Feb 09 2023, 12:35:11 AM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-91713D53-1941-449A-ADEF-9D15FE2CCBB2_1_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-May-2015 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: j27hd DOI: https://doi.org/10.31003/USPNF_M54303_01_01
2

rS = peak response of misoprostol from the Diluted This impurity is included in the table for identification only, and it is not to be
reported or included in the total impurities for the Misoprostol Dispersion.
standard solution b Methyl (1S*,2R*,3R*)-3-hydroxy-2-[(E)-4-hydroxy-4-methyl-1-octenyl]-5-
CS = concentration of USP Misoprostol RS in the oxocyclopentaneheptanoate.
Diluted standard solution (µg/mL) c (E)-Methyl 7-[2-(4-hydroxy-4-methyloct-1-enyl)-5-oxocyclopent-1-enyl]
CU = nominal concentration of misoprostol in the heptanoate.
Sample solution (µg/mL) d Methyl 7-[(1R*,2S*)-2-[(E)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopent-3-
F = relative response factor (see Table 1) enyl]heptanoate.

Acceptance criteria: See Table 1. Disregard a peak from the SPECIFIC TESTS
Diluent, eluting at about 4 min, and any other peak • WATER DETERMINATION, Method Ic á921ñ
observed in the Blank. Sample: 300 mg
Analysis: Perform the test immediately after opening the
Table 1 sample container. Use the evaporation technique in which
Relative Relative Acceptance water is released and evaporated from the Sample by
Retention Response Criteria, heating it in an external oven at 105° and transferring it to
Name Time Factor NMT (%) the reaction cell with the aid of an inert gas.
12-Epimisoprostol 0.84 — —a
Acceptance criteria: NMT 1.0%

8-Epimisoprostolb 0.90 0.90 0.50 ADDITIONAL REQUIREMENTS

• PACKAGING AND STORAGE: Preserve in tight containers,
Misoprostol 1.0 — — protected from light, and store in a refrigerator.
B-Type misoprostol c 1.6 0.78 0.30 • LABELING: The label states that this article is not intended
for direct administration to humans or animals. Label it to

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A-Type misoprostold 1.9 2.6 0.50 indicate the nominal concentration or percentage of
Any other individual im- misoprostol in the Misoprostol Dispersion.
— • USP REFERENCE STANDARDS á11ñ
purity 1.0 0.1
USP Misoprostol RS
Total impurities — — 1.8
ci
a This is a process impurity in the manufacturing of misoprostol. It is controlled
in the misoprostol, which is the starting material for the Misoprostol Dispersion.
ffi
O

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