Fosamprenavir Calcium 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

Fosamprenavir Calcium Tablets contain an amount of fosamprenavir calcium (C₂₅H₃₄CaN₃O₉PS) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of fosamprenavir (C₂₅H₃₄CaN₃O₉PS).

2 IDENTIFICATION

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

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

3.1 Procedure

Buffer: 4.68 g/L of monobasic sodium phosphate dihydrate in water. Add 1.5 mL of phosphoric acid per 1 L of this solution.

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and Buffer (20:80)

Standard solution: 0.26 mg/mL of USP Fosamprenavir Calcium RS in Diluent. Sonicate to dissolve prior to final dilution, if necessary.

Sample solution: Nominally 0.28 mg/mL of fosamprenavir from Tablets in Diluent prepared as follows. Transfer an amount equivalent to 14 mg of fosamprenavir from finely powdered Tablets (NLT 20) to a 50-mL volumetric flask. Add about 40 mL of Diluent and sonicate to dissolve, if necessary. Dilute with Diluent to volume. Pass a portion of the solution through a suitable filter, and discard the first few milliliters of the filtrate.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 266 nm

Column: 4.6-mm x 15-cm; 3.5-μm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fosamprenavir (C₂₅H₃₄CaN₃O₉PS) 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 fosamprenavir from the Sample solution

r_S = peak response of fosamprenavir from the Standard solution

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

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

M_r1 = molecular weight of fosamprenavir, 585.61

M_r2 = molecular weight of fosamprenavir calcium, 623.67

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1

Medium: 0.02 M sodium acetate buffer, pH 3.5, prepared as follows. Dissolve 2.67 g of sodium acetate in 100 mL of water. Add 13.3 mL of glacial acetic acid and then dilute with water to 1000 mL; 900 mL.▲(ERR 1-Sep-2023)

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: 0.83 mg/mL of USP Fosamprenavir Calcium RS in Medium. Sonicate to dissolve prior to final dilution, if necessary.

Sample solution: Pass a portion of the solution under test through a suitable filter.

4.1.1 Instrumental conditions

Mode: UV

Analytical wavelength: 263 nm

Cell path length: 0.02 cm

Blank: Medium

4.1.2 System suitability

Sample: Standard solution

4.1.3 Suitability requirement

Relative standard deviation: NMT 2.0%

4.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fosamprenavir (C₂₅H₃₄CaN₃O₉PS) dissolved:

Result = (A_U/A_S) × C_S × V × (1/L) × (M_r1/M_r2) × 100

A_U = absorbance from the Sample solution

A_S = absorbance from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

M_r1 = molecular weight of fosamprenavir, 585.61

M_r2 = molecular weight of fosamprenavir calcium, 623.67

Tolerances: NLT 80% (Q) of the labeled amount of fosamprenavir (C₂₅H₃₄CaN₃O₉PS) is dissolved.

4.2 Test 2

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

Solution A: 10 N acetic acid solution prepared as follows. Dilute 145 mL of glacial acetic acid to 250 mL with water.

Medium: 0.25 M sodium acetate buffer, pH 3.5, prepared as follows. Dissolve 34 g of sodium acetate in 500 mL of water. Add 300 mL of Solution A. Adjust with Solution A if necessary to a pH of 3.5 and then dilute with water to 1000 mL; 900 mL, deaerated

Apparatus 2: 75 rpm

Time: 30 min

Solution B: Methanol and acetonitrile (60:40)

Buffer: Dissolve 3.14 g of ammonium formate in 1000 mL of water. Adjust with formic acid to a pH of 3.2.

Mobile phase: Solution B and Buffer (60:40)

Solution C: 1.5 mL/L of phosphoric acid in water

Diluent: Acetonitrile and Solution C (55:45)

Standard stock solution: 0.5 mg/mL of USP Fosamprenavir Calcium RS in Diluent. Sonicate to dissolve.

Standard solution: 0.1 mg/mL of USP Fosamprenavir Calcium RS from Standard stock solution in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Dilute with Medium to a concentration that is similar to that of the Standard solution.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 266 nm

Column: 4.6-mm × 25-cm; 5-μm packing L7

4.2.2 Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2.2 times the retention time of fosamprenavir

4.2.3 System suitability

Sample: Standard solution

4.2.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.2.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fosamprenavir (C₂₅H₃₄CaN₃O₉PS) dissolved:

Result = (r_U/r_S) × C_S × V x D x (M_r1/M_r2) × (1/L) × 100

r_U = peak response of fosamprenavir from the Sample solution

r_S = peak response of fosamprenavir from the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution

M_r1 = molecular weight of fosamprenavir, 585.61

M_r2 = molecular weight of fosamprenavir calcium, 623.67

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fosamprenavir (C₂₅H₃₄CaN₃O₉PS) is dissolved. (RB 1-Sep-2023)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities: Early-Eluting Impurities

Buffer, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.26 mg/mL of USP Fosamprenavir System Suitability Mixture RS in Diluent. Sonicate to dissolve prior to final dilution, if necessary.

Standard solution: 0.28 μg/mL of USP Fosamprenavir Calcium RS in Diluent. Sonicate to dissolve prior to final dilution, if necessary.

5.1.1 System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for fosamprenavir pyrophosphate and fosamprenavir n-propyl homolog are 0.7 and 0.8, respectively.]

5.1.2 Suitability requirements

Resolution: NLT 1.5 between fosamprenavir pyrophosphate and fosamprenavir n-propyl homolog, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

5.1.3 Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of any early-eluting impurity in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any impurity from the Sample solution

r_S = peak response of fosamprenavir from the Standard solution

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

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

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

^a (2R,3S)-3-Amino-1-[(4-amino-N-isobutylphenyl)sulfonamide]-4-phenylbutan-2-yl dihydrogen phosphate.

^b Exclude any individual unspecified impurity that elutes after fosamprenavir.

^c Total impurities include the sum of all impurities determined in Organic Impurities: Early-Eluting Impurities and Organic Impurities: Late-Eluting Impurities.

5.2 Organic Impurities: Late-Eluting Impurities

Buffer: 1.58 g/L of ammonium formate in water. Adjust with ammonia solution to a pH of 9.0.

Solution A: Acetonitrile and Buffer (19:81)

Solution B: Acetonitrile, tetrahydrofuran, and Buffer (45:5:50)

Solution C: 4.68 g/L of monobasic sodium phosphate dihydrate in water. Add 1.5 mL of phosphoric acid per 1 L of this solution.

Mobile phase: See Table 2.

Table 2

Diluent: Acetonitrile and Solution C (20:80)

System suitability solution: 0.26 mg/mL of USP Fosamprenavir System Suitability Mixture RS in Diluent. Sonicate to dissolve prior to final dilution, if necessary.

Standard solution: 0.28 μg/mL of USP Fosamprenavir Calcium RS in Diluent. Sonicate to dissolve prior to final dilution, if necessary.

Sample solution: Nominally 0.28 mg/mL of fosamprenavir from Tablets in Diluent prepared as follows. Transfer an amount equivalent to 14 mg of fosamprenavir from finely powdered Tablets (NLT 20) to a 50-mL volumetric flask. Add about 40 mL of Diluent and sonicate to dissolve, if necessary. Dilute with Diluent to volume. Pass a portion of the solution through a suitable filter, and discard the first few milliliters of the filtrate.

5.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 266 nm

Column: 4.6-mm × 15-cm; 3.5-μm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 μL

5.2.2 System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for fosamprenavir and fosamprenavir n-butyl isomer are 1.0 and 1.2, respectively.]

5.2.3 Suitability requirements

Resolution: NLT 2 between fosamprenavir and fosamprenavir n-butyl isomer, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

5.2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any late-eluting impurity in the portion of fosamprenavir calcium taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any impurity from the Sample solution

r_S = peak response of fosamprenavir from the Standard solution

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

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

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

^a(S)-Tetrahydrofuran-3-yl {(2S,3R)-4-[(4-amino-N-isobutylphenyl)sulfonamide]-3-hydroxy-1-phenylbutan-2-yl}carbamate.

^b Exclude any individual unspecified impurity that elutes before fosamprenavir.

^c Total impurities include the sum of all impurities determined in Organic Impurities: Early-Eluting Impurities and Organic Impurities: Late-Eluting Impurities.

6 ADDITIONAL REQUIREMENTS

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

Add the following:

Labeling: The labeling states the Dissolution test used only if Test 1 is not used. (RB 1-Sep-2023)

USP Reference Standards 〈11〉

USP Fosamprenavir Calcium RS

USP Fosamprenavir System Suitability Mixture RS

A mixture of fosamprenavir calcium, fosamprenavir pyrophosphate, fosamprenavir n-propyl homolog, and fosamprenavir n-butyl isomer. Other impurities may also be present.