Raltegravir Chewable 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 

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

IDENTIFICATION 

Change to read: 

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

Sample: Grind a Tablet, and use a suitable amount of the powdered Chewable 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. 

2 ASSAY 

Change to read: 

Procedure 

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

Solution A: Acetonitrile and Buffer (20:80) 

Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1 

Diluent: Acetonitrile and water (30:70) 

Standard solution: 0.11 mg/mL of USP Raltegravir Potassium RS in Diluent 

Sample stock solution: Nominally equivalent to 1 mg/mL of raltegravir from Chewable Tablets prepared as follows. Transfer NLT 10 Chewable Tablets to a suitable volumetric flask and dilute with Diluent to 20% of the flask volume. Stir the contents of the flask for about 10 min to break apart the Chewable Tablets. Dilute with Diluent to volume and stir the contents of the flask for about 1 h. Centrifuge a portion of the solution and use the supernatant for Sample solution preparation. 

Sample solution: Nominally 0.1 mg/mL of raltegravir from the Sample stock solution 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 

Column temperature: 40° 

Flow rate: 1 mL/min 

Injection volume: 15 µL 

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 Chewable Tablets taken:  

Result = (r_U/r_S) × (C_S/C_U) × (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)

M_r1 = molecular weight of raltegravir, 444.42  

M_r2 = molecular weight of raltegravir potassium, 482.51 

Acceptance criteria: 95.0%–105.0% 

3 PERFORMANCE TESTS 

Change to read: 

Dissolution 〈711〉 

Medium: Water; 900 mL, deaerated 

Apparatus 2: 50 rpm 

Time: 15 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 (30:70) 

Standard solution: (L/900) mg/mL of raltegravir from USP Raltegravir Potassium RS in Diluent, where L is the label claim in mg/Chewable Tablet 

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: 30 µL 

Run time: 1 min 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

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 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) 

L = label claim (mg/Chewable Tablet) 

V = volume of Medium, 900 mL 

D = dilution factor for the Sample solution, if applicable 

M_r1 = molecular weight of raltegravir, 444.42  

M_r2 = molecular weight of raltegravir potassium, 482.51 

Tolerances: NLT 85% (Q) of the labeled amount of raltegravir is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

4 IMPURITIES 

Change to read: 

Organic Impurities 

Solution A, Mobile phase, 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: 0.22 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 2 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 Chewable Tablets taken: 

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

M_r1 = molecular weight of raltegravir, 444.42  

M_r2 = molecular weight of raltegravir potassium, 482.51 

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. Reporting threshold is 0.1%. 

Table 2 

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 included in total impurities. 

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. 

5 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. C₂₀H₂₂FN₆O₅ 426.43