Prasugrel Tablets

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

Prasugrel Tablets contain an amount of prasugrel hydrochloride (C₂₀H₂₀FNO₃S · HCl) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of prasugrel (C₂₀H₂₀FNO₃S).

2 IDENTIFICATION

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

B. The UV spectrum 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: Acetonitrile and 0.1% phosphoric acid (30:70)

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 0.55 mg/mL of USP Prasugrel Hydrochloride RS in Diluent prepared as follows. Transfer an appropriate amount of USP Prasugrel Hydrochloride RS to a suitable volumetric flask. Add Diluent to about 70% of the volume of the flask and sonicate. Dilute with Diluent to volume.

Standard solution: 0.055 mg/mL of USP Prasugrel Hydrochloride RS from Standard stock solution in Diluent. Pass a portion of the solution through a suitable filter of 0.45-µm pore size and use the filtrate.

Sample stock solution: Nominally equivalent to 0.5 mg/mL of prasugrel prepared as follows. Transfer Tablets (NLT 10) to an appropriate volumetric flask, add Diluent to about 75% of the nal volume of the flask, and sonicate with intermittent shaking to disperse the Tablets completely. Continue mixing with a suitable magnetic stirrer for 30 min. Dilute with Diluent to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size and use the filtrate.

Sample solution: Nominally equivalent to 0.05 mg/mL of prasugrel from Sample stock solution in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2.9 times the retention time of prasugrel

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of prasugrel (C₂₀H₂₀FNO₃S) in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (M_r1 /M_r2 ) × 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 = nominal concentration of prasugrel in the Sample solution (mg/mL)

M_r1 = molecular weight of prasugrel, 373.44

M_r2 = molecular weight of prasugrel hydrochloride, 409.90

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1 (RB 1-Aug-2021)

Solution A: 0.023 M citric acid prepared by dissolving 4.83 g of citric acid in 1000 mL of water

Solution B: 0.026 M dibasic sodium phosphate anhydrous prepared by dissolving 3.69 g of dibasic sodium phosphate anhydrous in 1000 mL of water

Medium: Solution A and Solution B (50:50). Adjust with Solution A or Solution B to a pH of 4.0; 900 mL

Apparatus 2: 75 rpm

Time: 20 min

Mobile phase: Acetonitrile and 0.1% phosphoric acid (30:70)

Standard stock solution: 0.3 mg/mL of USP Prasugrel Hydrochloride RS in acetonitrile. Sonicate to dissolve. Standard solution

For Tablets labeled to contain 5 mg/Tablet: 0.003 mg/mL of USP Prasugrel Hydrochloride RS prepared as follows. Dilute 4 mL of Standard stock solution with Medium to 200 mL in a suitable container and mix. Immediately dilute 5 mL of this solution with acetonitrile to 10 mL. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

For Tablets labeled to contain 10 mg/Tablet: 0.006 mg/mL of USP Prasugrel Hydrochloride RS prepared as follows. Dilute 4 mL of Standard stock solution with Medium to 100 mL in a suitable container and mix. Immediately dilute 5 mL of this solution with acetonitrile to 10 mL. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Immediately dilute 5 mL of this solution with acetonitrile to 10 mL.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 2.6 times the retention time of prasugrel

4.1.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of prasugrel (C₂₀H₂₀FNO₃S) dissolved:

Result = (r_U /r_S ) × C_S × V × (M_r1 /M_r2 ) × (1/L) × 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)

V = volume of Medium, 900 mL

M_r1 = molecular weight of prasugrel, 373.44

M_r2 = molecular weight of prasugrel hydrochloride, 409.90

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of prasugrel (C₂₀H₂₀FNO₃S) is dissolved.

4.2 Test 2

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium: Citrate phosphate buffer pH 4.0 (Dissolve 4.63 g of dibasic sodium phosphate dihydrate and 4.83 g of citric acid in l000 mL of water. Adjust with 0.2 M dibasic sodium phosphate dihydrate or 0.1 M citric acid monohydrate to a pH of 4.0.); 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer A: Dissolve 1.36 g of monobasic potassium phosphate in 1000 mL of water. Adjust with 5% sodium hydroxide solution to a pH of 6.5.

Buffer B: Dissolve 1.36 g of monobasic potassium phosphate in 1000 mL of water. Adjust with 1% phosphoric acid to a pH of 4.0. Mobile phase: Acetonitrile and Buffer B (85:15)

Diluent: Acetonitrile and Buffer A (50:50)

Standard stock solution: 0.25 mg/mL of USP Prasugrel Hydrochloride RS in Diluent. Sonicate to dissolve.

Standard solution

For Tablets labeled to contain 5 mg/Tablet: 0.002 mg/mL of USP Prasugrel Hydrochloride RS prepared as follows. Dilute 5 mL of Standard stock solution with Medium to 200 mL. Dilute 5 mL of this solution with Diluent to 15 mL.

For Tablets labeled to contain 10 mg/Tablet: 0.004 mg/mL of USP Prasugrel Hydrochloride RS prepared as follows. Dilute 5 mL of Standard stock solution with Medium to 100 mL. Dilute 5 mL of this solution with Diluent to 15 mL.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Discard NLT 7 mL of filtrate. Immediately dilute 5 mL of this solution with Diluent to 15 mL.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 205 nm

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

Temperatures

Autosampler: 7°

Column: 40°

Flow rate: 1 mL/min

Injection volume: 50 µL

Run time: NLT 1.5 times the retention time of prasugrel

4.2.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8–2.0

Relative standard deviation: NMT 2.0%

4.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of prasugrel (C₂₀H₂₀FNO₃S) dissolved:

Result = (r_U /r_S ) × C_S × V × (M_r1 /M_r2 ) × D × (1/L) × 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)

V = volume of Medium, 900 mL

M_r1 = molecular weight of prasugrel, 373.44

M_r2 = molecular weight of prasugrel hydrochloride, 409.90

D = dilution factor, 3

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of prasugrel (C₂₀H₂₀FNO₃S) is dissolved. (RB 1-Aug-2021)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities, Procedure 1

Solution A: 2.72 g of monobasic potassium phosphate in 1000 mL of 0.1% phosphoric acid

Solution B: Acetonitrile and methanol (90:10)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.011 mg/mL of USP Prasugrel Hydrochloride RS in Diluent. Sonication may be needed to dissolve. Sensitivity solution: 0.5 µg/mL of USP Prasugrel Hydrochloride RS from Standard solution in Diluent

Sample solution: Nominally equivalent to 1 mg/mL of prasugrel prepared as follows. Transfer a portion of finely powdered Tablets (NLT 10), equivalent to 25 mg of prasugrel, to a 25-mL volumetric flask. Add 15 mL of Diluent and sonicate for 10 min with intermittent shaking while maintaining at 20°. Dilute with Diluent to volume and pass the solution through a suitable filter of 0.45-µm pore size. This solution should be prepared fresh and injected immediately.

5.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detectors

For prasugrel: UV 220 nm

For prasugrel diketone: UV 252 nm

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

Column temperature: 35°

Flow rate: 1.6 mL/min

Injection volume: 20 µL

5.1.2 System suitability

Samples: Standard solution and Sensitivity solution

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

Suitability requirements

Tailing factor: NMT 2.0 at 220 and 252 nm, Standard solution

Relative standard deviation: NMT 5.0% at 220 and 252 nm, Standard solution

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

5.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any specified or unspecified degradation products in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × (M_r1 /M_r2 ) × 100

r_U = peak response of each corresponding degradation product 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 = nominal concentration of prasugrel in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

M_r1 = molecular weight of prasugrel, 373.44

M_r2 = molecular weight of prasugrel hydrochloride, 409.90

Calculate the percentage of prasugrel diketone in the portion of Tablets taken (at 252 nm):

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × (M_r1 /M_r2 ) × 100

r_U = peak response of prasugrel diketone 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 = nominal concentration of prasugrel in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

M_r1 = molecular weight of prasugrel, 373.44

M_r2 = molecular weight of prasugrel hydrochloride, 409.90

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

Table 2

a 5,6,7,7a-Tetrahydrothieno[3,2-c]pyridin-2(4H)-one.

b Both thienotetrahydropyridinone and acetylthienotetrahydropyridine are analyzed by Organic Impurities, Procedure 2.

c 4,5,6,7-Tetrahydrothieno[3,2-c]pyridin-2-yl acetate.

d (Z)-2-(1-(2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4-mercaptopiperidin-3-ylidene) acetic acid.

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-(2-fluorophenyl)-2-oxoethyl]-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one. Desacetyl prasugrel diastereoisomer-1 and desacetyl prasugrel diastereoisomer-2 are a pair of diastereomers.

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

h Include all impurities from Organic Impurities, Procedure 1 and Organic Impurities, Procedure 2.

5.2 Organic Impurities, Procedure 2

Solution A: Transfer 1.0 mL of perchloric acid (about 70%) to 1000 mL of water.

Solution B: Acetonitrile

Mobile phase: See Table 3.

Table 3

Diluent: Acetonitrile and water (25:75)

Standard stock solution: 1.1 mg/mL of USP Prasugrel Hydrochloride RS in Diluent prepared as follows. Transfer an appropriate amount of USP Prasugrel Hydrochloride RS to a suitable volumetric flask. Add Diluent to about 60% of the volume of the ask and sonicate. Dilute with Diluent to volume. Pass the solution through a suitable filter of 0.45-µm pore size.

Standard solution: 0.011 mg/mL of USP Prasugrel Hydrochloride RS from Standard stock solution in Diluent

Sample solution: Nominally equivalent to 1 mg/mL of prasugrel prepared as follows. Transfer a portion of finely powdered Tablets (NLT 10), equivalent to about 25 mg of prasugrel, to a 25-mL volumetric flask. Add 15 mL of Diluent and sonicate for 10 min with intermittent shaking while maintaining at 20°. Dilute with Diluent to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

5.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 5-µm packing L11

Column temperature: 20°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

5.2.2 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

5.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified degradation product in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U ) × (1/F) × (M_r1 /M_r2 ) × 100

r_U = peak response of each specified degradation product 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 = nominal concentration of prasugrel hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 4)

M_r1 = molecular weight of prasugrel, 373.44

M_r2 = molecular weight of prasugrel hydrochloride, 409.90

Acceptance criteria: See Table 4.

Table 4

6 ADDITIONAL REQUIREMENTS

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

Add the following:

Labeling: When more than one Dissolution test is given, the Labeling states the test used only if Test 1 is not used. (RB 1-Aug-2021)

USP Reference Standards 〈11〉

USP Prasugrel Hydrochloride RS (USP 1-Aug-2021)