Indinavir Sulfate

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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C₃₆H₄₇N₅O₄ . H₂SO₄  711.87

d-erythro-Pentonamide, 2,3,5-trideoxy-N-(2,3-dihydro-2-hydroxy-1H-inden-1-yl)-5-[2-[[(1,1-dimethylethyl)amino] carbonyl]-4-(3-pyridinylmethyl)-1-piperazinyl]-2-(phenylmethyl)-, [1(1S,2R),5(S)]-, sulfate (1:1) (salt);

(αR,γS,2S)-α-Benzyl-2-(tert-butylcarbamoyl)-γ-hydroxy-N-[(1S,2R)-2-hydroxy-1-indanyl]-4-(3-pyridylmethyl)-1-piperazinevaleramide sulfate (1:1) (salt)

CAS RN^®: 157810-81-6; UNII: 771H53976Q.

1 DEFINITION

Indinavir Sulfate contains NLT 98.5% and NMT 101.5% of C₃₆H₄₇N₅O₄ . H₂SO₄, calculated on the anhydrous, solvent-free basis.

IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M (CN 1-MAY-2020) Maxima at about 3.0-3.1, 5.9, 6.2, and 13.6 µm

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

C. IDENTIFICATION TESTS-GENERAL, Sulfate(191): Meets the requirements

Sample solution: A solution of 10 mg/mL in water

2 ASSAY

2.1 PROCEDURE

Solution A: Dibutyl ammonium phosphate and water (1:50). Adjust with sodium hydroxide TS to a pH of 6.5 ± 0.5.

Mobile phase: Acetonitrile and Solution A (9:11)

Standard solution: 0.5 mg/mL of USP Indinavir RS in Mobile phase

Sample solution: 0.6 mg/mL of Indinavir Sulfate in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 4000 theoretical plates

Tailing factor: Less than 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₃₆H₄₇N₅O₄ . H₂SO₄ in the portion taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Indinavir Sulfate in the Sample solution (mg/mL)

M_U = molecular weight of indinavir sulfate, 711.87

M_S = molecular weight of indinavir, 613.79

Acceptance criteria: 98.5%–101.5% on the anhydrous, solvent-free basis

3 OTHER COMPONENTS

3.1 PROCEDURE 1: CONTENT OF SULFATE

Solution A: Methanol and formaldehyde (1000:0.3)

Diluent: Solution A and water (1:1)

Sample solution: 6.25 mg/mL of Indinavir Sulfate in Diluent

Analysis: Titrate with 0.1 M lead perchlorate VS, using a lead-specific electrode in conjunction with a suitable reference electrode. Each mL of 0.1 M lead perchlorate VS is equivalent to 9.604 mg of sulfate.

Acceptance criteria: 13.2%–14.4%, calculated on the anhydrous and solvent-free basis

3.2 PROCEDURE 2: CONTENT OF ALCOHOL

Standard solution: 0.001 mL/mL of dehydrated alcohol, in water.

[Note-Dehydrated alcohol is at 20°.]

Sample solution: 4 mg/mL of Indinavir Sulfate in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m capillary column with a 1.0-µm film of phase G16

Temperature

Column: 35°

Injector: 140°

Detector: 220°

[Note-At the end of each 5-min isothermal run, increase the oven temperature to 200° before adjusting the column temperature to 35° for the next injection.]

Flow rate: 10 mL/min

Carrier gas: Helium

Injection size: 0.1 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of alcohol in the portion of Indinavir Sulfate taken:

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

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

C_S = concentration of dehydrated alcohol in the Standard solution (mL/mL)

C_U = concentration of Indinavir Sulfate in the Sample solution (mg/mL)

D = density of alcohol at 20°, 790 mg/mL

Acceptance criteria: 5.0%-8.0%

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

PROCEDURE

Solution A: 0.27 g/L of monobasic potassium phosphate and 1.395 g/L of dibasic potassium phosphate, in water

Solution B: Acetonitrile

Mobile phase: See the gradient table below.

Diluent: Solution A and Solution B (1:1)

System suitability solution: 0.4 mg/mL of USP Indinavir System Suitability RS in Diluent

Sample solution: 0.5 mg/mL of Indinavir Sulfate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.8 between indinavir and indinavir related compound C

Tailing factor: More than 0.95 and less than 2.0, determined from the indinavir peak

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Indinavir Sulfate taken:

Result = (r_U/r_T) × 100

r_U = peak area response for each impurity

r_T = sum of the responses of all the peaks

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.5%

Impurity Table 1

^a (1S,2R)-1-Aminoindan-2-ol.

^b (S)-1-{(2S,4R)-4-Benzyl-2-hydroxy-5-[(1S,2R)-2-hydroxyindan-1-ylamino]-5-oxopentyl}-N-tert-butylpiperazine-2-carboxamide.

^c (S)-1-{(2R,4R)-4-Benzyl-2-hydroxy-5-[(1S,2R)-2-hydroxyindan-1-ylamino]-5-oxopentyl}-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide.

^d (S)-1-{[(2S,4R)-4-Benzyl-5-oxotetrahydrofuran-2-yl]methyl}-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide.

^e (2R,2′R,4S,4′S)-5,5′-[(S)-2-(tert-Butylcarbamoyl)piperazine-1,4-diyl]bis{2-benzyl-4-hydroxy-N-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]pentanamide}.

5 SPECIFIC TESTS

OPTICAL ROTATION, Specific Rotation(781S): +122° to +129°, at 365 nm, determined on the anhydrous, solvent-free basis

Sample solution: 10 mg/mL in water

WATER DETERMINATION, Method / (921): NMT 1.5%, using 0.25 g

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, protected from moisture. Store at 25°, excursions permitted between 15° and 30°.

USP REFERENCE STANDARDS (11)

USP Indinavir RS

USP Indinavir System Suitability RS