Raltegravir 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 

Change to read: 

Raltegravir Tablets contain an amount of Raltegravir Potassium equivalent to NLT 95.0% and NMT 105.0% of the labeled amount of raltegravir (C₂₀H₂₁FN₆O₅).

2 IDENTIFICATION 

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A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K (CN 1-May-2020)

Sample: Grind a Tablet, and use a suitable amount of the powdered Tablet to prepare a specimen. 

Acceptance criteria: The spectrum obtained from the Sample shows bands at approximately 1633, 1515, 1188, 810, and 728 cm−1, similar to 

the spectrum from the Standard similarly obtained. [Note—Peak positions may vary slightly between instruments (within ±10 cm−1). Other peaks may be present in the spectra that do not appear in this list.] 

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 

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Procedure 

Buffer: 1.36 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.5. 

Mobile phase: Acetonitrile and Buffer (29:71) 

Solution A: Acetonitrile and water (50:50) 

Diluent: Acetonitrile and water (30:70) 

Standard solution: 0.22 mg/mL of USP Raltegravir Potassium RS in Diluent 

Sample stock solution: Nominally equivalent to 8 mg/mL of raltegravir from Tablets prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask and dilute with Solution A to volume. Stir the flask vigorously for 1 h. Centrifuge a portion of the solution and use the supernatant for Sample solution preparation. 

Sample solution: Nominally 0.2 mg/mL of raltegravir in Diluent from Sample stock solution 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 210 nm 

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

Column temperature: 40° 

Flow rate: 2 mL/min 

Injection volume: 30 µL 

Run time: NLT 1.5 times the retention time of raltegravir 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 1.5 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of raltegravir (C₂₀H₂₁FN₆O₅) in the portion of Tablets taken: 

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

r_U = peak response of raltegravir from the Sample solution 

r_S = peak response of raltegravir from the Standard solution 

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

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

L = label claim (mg/Tablet) 

V = volume of Medium, 900 mL 

D = dilution factor for the Sample solution, if needed 

M_r1 = molecular weight of raltegravir, 444.42 

M_r2 = molecular weight of raltegravir potassium, 482.51 

Acceptance criteria: 95.0%–105.0% 

4 PERFORMANCE TESTS 

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Dissolution 〈711〉 

Medium: Water; 900 mL, deaerated 

Apparatus 2: 100 rpm with sinker 

Times: 15 and 60 min 

Buffer: 1.36 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0. 

Mobile phase: Acetonitrile and Buffer (38:62) 

Diluent: Acetonitrile and water (20:80) 

Standard solution: 0.48 mg/mL of USP Raltegravir Potassium RS in Diluent. Sonicate, if necessary, to dissolve prior to nal dilution. Sample solution: Pass a portion of the solution under test through a suitable filter. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 303 nm 

Column: 4.6-mm × 10-cm; packing L1 

Column temperature: 40° 

Flow rate: 5 mL/min 

Injection volume: 10 µL 

Run time: 1 min 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 3.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of raltegravir (C₂₀H₂₁FN₆O₅) dissolved: 

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

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

C = concentration of the USP Raltegravir Potassium RS in the Standard solution (mg/mL) 

L = label claim (mg/Tablet) 

V = volume of Medium, 900 mL 

D = dilution factor for the Sample solution, if needed 

M_r1 = molecular weight of raltegravir, 444.42 

M_r2 = molecular weight of raltegravir potassium, 482.51 

Tolerances: 15%–45% of the labeled amount of raltegravir is dissolved in 15 min, and NLT 70% (Q) of the labeled amount of raltegravir is dissolved in 60 min. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

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Organic Impurities 

Buffer, Mobile phase, Solution A, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay. Peak identification solution: Prepare a solution containing 2 mg/mL of USP Raltegravir Potassium RS in 1 N sodium hydroxide solution. Stir the solution for 2 h at room temperature. Transfer 5 mL of this solution to a 50-mL volumetric flask and add 5 mL of 1 N hydrochloric acid. Dilute with Diluent to volume. [Note—In situ degradation generates the raltegravir amine and raltegravir oxalylacetohydrazide analog peaks along with a small peak for raltegravir oxalyl analog impurity.] 

System suitability solution: 0.1 mg/mL of USP Raltegravir Potassium RS and 0.2 µg/mL of USP Raltegravir Related Compound E RS in Diluent Standard stock solution: Use the Standard solution prepared in the Assay. 

Standard solution: 0.44 µg/mL of USP Raltegravir Potassium RS in Diluent from Standard stock solution 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—See Table 1 for relative retention times.] 

Suitability requirements 

Resolution: NLT 1.5 between raltegravir related compound E and raltegravir, System suitability solution 

Relative standard deviation: NMT 10.0%, Standard solution 

Analysis 

Samples: Sample solution, Peak identification solution, and Standard solution 

Calculate the percentage of any individual impurity in the portion of Tablets taken: 

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

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

r_S = peak response of raltegravir from the Standard solution 

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

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

M_r1 = molecular weight of raltegravir, 444.42 

M_r2 = molecular weight of raltegravir potassium, 482.51 

F = relative response factor (see Table 1) 

Acceptance criteria: See Table 1. Reporting threshold is 0.1%. 

Table 1 

a 2-(2-Aminopropan-2-yl)-N-(4-uorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide.

b This is a process impurity controlled in the drug substance and not monitored in the drug product. 

c(E)-2-(2-{[(Dimethylamino)methylidene]amino}propan-2-yl)-N-(4-uorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4- carboxamide. 

d 2-[(2-{4-[(4-Fluorobenzyl)carbamoyl]-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl}propan-2-yl)amino]-2-oxoacetic acid. e 2-{2-[2-(2-Acetylhydrazinyl)-2-oxoacetamido]propan-2-yl}-N-(4-uorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4- carboxamide. 

6 ADDITIONAL REQUIREMENTS 

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

USP Reference Standards 〈11〉 

USP Raltegravir Potassium RS 

USP Raltegravir Related Compound E RS 

N-{2-[4-(Benzylcarbamoyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl]propan-2-yl}-5-methyl-1,3,4-oxadiazole-2-carboxamide. C₂₀H₂₂N₆O₅426.43