Saquinavir Mesylate

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

Saquinavir Mesylate contains NLT 98.5% and NMT 101.0% of saquinavir mesylate (C₃₈H₅₀N₆O₅ · CH₄O₃S), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K ▲or 197A▲ (USP 1-Dec-2022)

Delete the following:

▲B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy▲ (USP 1-Dec-2022)

Change to read:

▲B.▲ (USP 1-Dec-2022) 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

Change to read:

Procedure

Buffer: Transfer 10 mL of triethylamine to a 1 L flask, and dilute with water to volume. Adjust with phosphoric acid to a pH of 2.5.

Mobile phase: Acetonitrile, tetrahydrofuran, and Buffer (5:25:70). [Note—Protect from light.]

System suitability solution: 0.25 mg/mL of USP Saquinavir Mesylate RS and 0.002 mg/mL of USP Saquinavir Related Compound A RS in

Mobile phase

Standard solution: 0.25 mg/mL of USP Saquinavir Mesylate RS in Mobile phase

Sample solution: 0.25 mg/mL of Saquinavir Mesylate in Mobile phase, and mix for about 20 min

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; packing L1

Column temperature: 20°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for saquinavir related compound A and saquinavir are 0.89 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between saquinavir related compound A and saquinavir, System suitability solution

▲Tailing factor: NMT 2.0, Standard solution▲ (USP 1-Dec-2022)

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of saquinavir mesylate (C₃₈H₅₀N₆O₅ · CH₄O₃S) in the portion of Saquinavir Mesylate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of saquinavir from the Sample solution

rₛ = peak response of saquinavir from the Standard solution

Cₛ = concentration of USP Saquinavir Mesylate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Saquinavir Mesylate in the Sample solution (mg/mL)

Acceptance criteria: 98.5%–101.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

Organic Impurities

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

the Assay.

▲Sensitivity solution: 0.125 µg/mL of USP Saquinavir Mesylate RS in Mobile phase▲ (USP 1-Dec-2022)

System suitability

Samples: System suitability solution, Standard solution, ▲and Sensitivity solution▲ (USP 1-Dec-2022)

[Note—The relative retention times for saquinavir related compound A and saquinavir are 0.89 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between saquinavir related compound A and saquinavir, System suitability solution

▲Tailing factor: NMT 2.0, Standard solution▲ (USP 1-Dec-2022)

Relative standard deviation: NMT 2.0%, Standard solution

▲Signal-to-noise-ratio: NLT 10, Sensitivity solution▲ (USP 1-Dec-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Saquinavir Mesylate taken:

Result = (rᵢ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵢ = peak response of any individual impurity from the Sample solution

rₛ = peak response of saquinavir from the Standard solution

Cₛ = concentration of USP Saquinavir Mesylate RS in the Standard solution (mg/mL)

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

F = relative response factor (see Table 1)

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

Table 1

ᵃ (3S,4aS,8aS)-2-[(2R,3S)-3-Amino-2-hydroxy-4-phenylbutyl]-N-(tert-butyl)decahydroisoquinoline-3-carboxamide.

ᵇ (Quinoline-2-carbonyl)-l-asparagine.

ᶜ Ethyl (quinoline-2-carbonyl)-l-asparaginate.

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 5 mg/mL in methanol

Acceptance criteria: −66.8° to −69.6° (λ = 436 nm at 20°)

Water Determination 〈921〉, Method I: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Saquinavir Mesylate RS

USP Saquinavir Related Compound A RS

▲N₁-{(2S,3R)-3-Hydroxy-4-[(3S,4aS,8aS)-3-[(2-methyl-2-propanyl)carbamoyl]octahydro-2(1H)-isoquinolinyl]-1-phenylbutan-2-yl}-N₂-(quinoline-

2-carbonyl)-d-asparaginamide.▲ (USP 1-Dec-2022)

C₃₈H₅₀N₆O₅ ▲670.86▲ (USP 1-Dec-2022)