Prasugrel Hydrochloride

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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C₂₀H₂₀FNO₃S · HCl 409.90

Ethanone, 2-[2-(acetyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)-, hydrochloride; 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate hydrochloride CAS RN®: 389574-19-0;

UNII: G89JQ59I13. Prasugrel (free base)

C₂₀H₂₀FNO₃S      373.44 CAS RN®: 150322-43-3; UNII: 34K66TBT99. (USP 1-Aug-2023)

1 DEFINITION

Prasugrel Hydrochloride contains NLT 97.0% and NMT 102.0% of prasugrel hydrochloride (C₂₀H₂₀FNO₃S · HCl), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A

Change to read:

B. The retention time of the major (USP 1-Aug-2023) peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride: Meets the requirements

3 ASSAY

Change to read:

Procedure

Buffer: 10 mM monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.8.

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and water (70:30)

Standard solution: 0.1 mg/mL of USP Prasugrel Hydrochloride RS in Diluent

Sample solution: 0.1 mg/mL of Prasugrel Hydrochloride in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2.5 times the retention time of prasugrel

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0 (USP 1-Aug-2023)

Relative standard deviation: NMT 0.73% (USP 1-Aug-2023)

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of prasugrel hydrochloride (C₂₀H₂₀FNO₃S · HCl) in the portion of Prasugrel Hydrochloride taken:

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

r_U = peak response of prasugrel from the Sample solution

r_S = peak response of prasugrel from the Standard solution

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

C_U = concentration of Prasugrel Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Delete the following:

Organic Impurities, Procedure 1 (USP 1-Aug-2023)

Delete the following:

Organic Impurities, Procedure 2 (USP 1-Aug-2023) Add the following:

Organic Impurities

Buffer: 3 mL of phosphoric acid in 1000 mL of water. Adjust with 10% (w/v) potassium hydroxide solution to a pH of 2.9. Solution A: Buffer

Solution B: Acetonitrile and water (90:10)

Mobile phase: See Table 1.

Table 1

System suitability solution: 1.5 mg/mL of USP Prasugrel Hydrochloride RS and 7.5 µg/mL of USP Prasugrel Related Compound D RS in Solution B

Standard solution: 1.5 µg/mL of USP Prasugrel Hydrochloride RS in Solution B

Sensitivity solution: 0.75 µg/mL of USP Prasugrel Hydrochloride RS from the Standard solution in Solution B Sample solution: 1.5 mg/mL of Prasugrel Hydrochloride in Solution B

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 20 µL

4.2 System suitability

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

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between the desacetyl prasugrel diastereomer 1 and desacetyl prasugrel diastereomer 2, System suitability solution Relative standard deviation: NMT 5.0%, Standard solution

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

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified or any unspecified impurity in the portion of Prasugrel Hydrochloride taken:

Result = (r_U /r ) × (C /C_U ) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of prasugrel from the Standard solution

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

C_U = concentration of Prasugrel Hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

a 5-(2-Cyclopropyl-2-oxo-1-phenylethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate.

b 5-[1-(2-Fluorophenyl)-2-oxopropyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)acetate.

c 1-Cyclopropyl-2-[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-2-(2-fluorophenyl)ethan-1-one.

d 5-[2-Cyclopropyl-1-(4-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate.

e 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-7a-hydroxy-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one.

f 5-[2-Cyclopropyl-1-(3-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate.

g 1-Cyclopropyl-2-(2-fluorophenyl)ethane-1,2-dione.

h 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one hydrochloride. It is a mixture of diastereomers and shows two peaks in HPLC.

i 5-[5-Chloro-1-(2-fluorophenyl)-2-oxopentyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate.

 (USP 1-Aug-2023)

5 SPECIFIC TESTS

Change to read:

Water Determination 〈921〉, Method I,Method Ia (USP 1-Aug-2023) or Method Ic: NMT 0.50%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Prasugrel Hydrochloride RS

USP Prasugrel Related Compound D RS

5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one. [Note—This contains desacetyl prasugrel diastereomer 1 and desacetyl prasugrel diastereomer 2 in free base.]

C₁₈H₁₈FNO₂S        331.41 (USP 1-Aug-2023)