Published on USP Medicines Compendium (https://mc.usp.

org)

Etoricoxib Proposed For Comment Version 1.1

C18H15ClN2O2S

358.84

2,3-Bipyridine, 5-chloro-6-methyl-3-[4-(methylsulfonyl)phenyl]-; 5-Chloro-6-methyl-3-[p-(methylsulfonyl)phenyl]-2,3-bipyridine [202409-33-4]. Etoricoxib is a white to off-white powder. It is freely soluble in methanol, in tetrahydrofuran, in dimethyl sulfoxide, in dimethyl formamide, and in chloroform; soluble in ethanol and in toluene; practically insoluble in water. [NOTESample solution to be protected from light.]

Performance-Based Monograph (Contains tests, procedures, and acceptance criteria for the material under test. It also includes the criteria-based procedures to demonstrate that an Acceptable Procedure is equivalent to the Reference Procedures.)

DEFINITION Etoricoxib contains NLT 98.0% and NMT 102.0% of etoricoxib (C18H15ClN2O2S), calculated on the anhydrous basis. IDENTIFICATION A. INFRARED ABSORPTION <197K> ASSAY PROCEDURE Standard solution: USP Etoricoxib RS in an appropriate diluent Sample solution: Etoricoxib in an appropriate diluent Analytical system: Use a procedure validated as described in MC general chapter Assessing Validation Parameters for Reference and Acceptable Procedures <10>. System performance requirements Precision: Meets the requirements for 98.0%102.0% Accuracy: Meets the requirements for 98.0%102.0% Specificity: Meets the requirements Range: Meets the requirements Analysis Samples: Standard solution and Sample solution

Calculate the percentage of etoricoxib (C18H15ClN2O2S) in the Sample solution: Result = (rU/rS) (CS/CU) 100 rU rS = response from the Sample solution = response from the Standard solution

CS = concentration of the Standard solution CU = concentration of the Sample solution Acceptance criteria: 98.0%102.0% on the anhydrous basis IMPURITIES RESIDUE
ON IGNITION

<281>: NMT 0.1%

ELEMENTAL IMPURITIES <232>: Proceed as directed in the chapter. RESIDUAL SOLVENTS <467>: Proceed as directed in the chapter. ORGANIC IMPURITIES Standard solution: USP Etoricoxib RS and all appropriate USP Impurity RSs, at concentrations corresponding to the Acceptance criteria of the impurity, in an appropriate diluent Sample solution: Etoricoxib in an appropriate diluent Analytical system: Use a procedure validated as described in MC general chapter Assessing Validation Parameters for Reference and Acceptable Procedures <10>. System performance requirements Accuracy: Meets the requirements Precision: Meets the requirements Ruggedness: Meets the requirements Specificity: Meets the requirements Analysis Samples: Standard solution and Sample solution Calculate the percentage of each impurity in the Sample solution: Result = (rU/rS) (CS/CU) 100 rU = response of each impurity from the Sample solution rS = response of each USP Impurity RS from the Standard solution. [NOTEIf no USP Impurity RSs are available, use the response of etoricoxib.] CS CU = concentration of standard material in the Standard solution = concentration of Etoricoxib in the Sample solution

Acceptance criteria Any individual impurity: NMT 0.10% Total impurities: NMT 2.0% SPECIFIC TESTS WATER DETERMINATION, Method I <921>: NMT 1.0% ADDITIONAL REQUIREMENTS REFERENCE STANDARDS <11> USP Etoricoxib RS [1] USP Etoricoxib Impurity A RS (Use USP Etoricoxib Related Compound A RS [2].) 4-Methylsulfonyl acetophenone. USP Etoricoxib Impurity B RS (Use USP Etoricoxib Related Compound B RS [3].) 4-(Methylsulfonyl)-phenyl acetic acid. USP Etoricoxib Impurity C RS (Use USP Etoricoxib Related Compound C RS [4].) 2-Chloro-1,3-bis(dimethylamino) trimethinium hexafluorophosphate. USP Etoricoxib Impurity D RS

1-(6-Methylpyridine-3-yl)-2-[(4-methylsulfonyl)phenyl]ethanone. USP Etoricoxib Impurity E RS 6-Methyl(pyridine-3-carboxylic acid)methyl ester.

REFERENCE PROCEDURES (This section provides detailed descriptions of procedures that may be used for the evaluation of the material under test. These procedures have been fully validated, and the data is available on the MC website.)

ASSAY PROCEDURE [NOTEThe Standard and Sample solutions should be protected from light.] Solution A: 10 mM ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.0. Diluent: Solution A and acetonitrile (3:1) Mobile phase: Solution A and acetonitrile (13:7) Standard solution: 0.1 mg/mL of USP Etoricoxib RS in Diluent Sample solution: 0.1 mg/mL of Etoricoxib in Diluent Chromatographic system (See Chromatography <621>, System Suitability.) Mode: LC Detector: PDA (scan 200400 nm). [NOTECalculations should be based on the chromatograms collected at 234 nm.] Column: 4.6-mm 15-cm; 5-m packing L1 (similar to Hypersil BDS C18) Flow rate: 1 mL/min Injection volume: 10 L System suitability Sample: Standard solution Suitability requirements Relative standard deviation: NMT 1.0% for the etoricoxib peak Analysis Samples: Standard solution and Sample solution Calculate the percentage of etoricoxib (C18H15ClN2O2S) in the portion of Etoricoxib taken: Result = (rU/rS) (CS/CU) 100 rU = peak response of etoricoxib from the Sample solution rS = peak response of etoricoxib from the Standard solution CS = concentration of USP Etoricoxib RS in the Standard solution. [NOTEThe potency of the Reference Material is included in this term.] CU = concentration of Etorcoxib in the Sample solution IMPURITIES ORGANIC IMPURITIES [NOTEThe Standard and Sample solutions should be protected from light.] Solution A: 20 mM ammonium formate in water. Adjust with formic acid to a pH of 3.0. Solution B: 20 mM ammonium formate in water. Solution C: Solution A and acetonitrile (17:3) Solution D: Mix Solution B, acetonitrile, and 2-propanol (25:24:1) and adjust with formic acid to a pH of 4.0. Diluent: Solution A and methanol (1:1) Mobile phase: See Table 1. Table 1 Time (min) 0 Solution C (%) 100 Solution D (%) 0

5 8 10 14 15 18

100 40 20 20 100 100

0 60 80 80 0 0

System suitability solution: 0.03 mg/mL of USP Etoricoxib RS in Diluent Standard solution: 0.5 g/mL each of USP Etoricoxib RS, USP Etoricoxib Impurity A RS, USP Etoricoxib Impurity B RS, USP Etoricoxib Impurity C RS, USP Etoricoxib Impurity D RS, and USP Etoricoxib Impurity E RS in Diluent Resolution solution: 5 g/mL each of USP Etoricoxib Impurity C RS and USP Etoricoxib Impurity E RS in Diluent Sample solution: 0.5 mg/mL of Etoricoxib in Diluent Chromatographic system (See Chromatography <621>, System Suitability.) Mode: UHPLC Detector: PDA and MS PDA wavelengths: 200400 nm. [NOTEWhere Reference Standards are available a peak maximum wavelength should be chosen for calculations, otherwise, calculations should be made at an isobestic point of the drug substance and impurity spectra or at 257 nm if an isobestic point is not available. Impurity C calculations should be done at 323 nm.] MS source: ES scan (+ and ) MS conditions Source temperature: 100 Desolvation temperature: 400 Column: 2.1-mm 10-cm; 1.7-m packing L11 (similar to Phenomenex Kinetex Phenyl Hexyl) Column oven temperature: 30 Flow rate: 0.2 mL/min Injection volume: 2 L System suitability Samples: System suitability solution, Standard solution, and Resolution solution Suitability requirements Resolution 1: NLT 3.0 between impurity A and impurity D peaks, Standard solution Resolution 2: NLT 3.0 between impurity C and impurity E peaks, Resolution solution Relative standard deviation: NMT 1.0% for the etoricoxib peak, System suitability solution Analysis Samples: Standard solution and Sample solution Calculate the percentage of each impurity in the portion of Etoricoxib taken: Result = (rU/rS) (CS/CU) 100 rU = peak response of each impurityfrom the Sample solution rS = peak response of each impurityfrom the Standard solution CS = concentration of each impurity in the Standard solution. [NOTEThe potency of the Reference Material is included in this term.] CU = concentration of Etorcoxib in the Sample solution

Source URL (modified on 2014/02/28 - 12:00am): https://mc.usp.org/monographs/etoricoxib-1-1