Development and Validation of an HPLC Method for the Impurity and Quantitative Analysis of Etoricoxib

Abstract

Etoricoxib (5‐chloro‐6′‐methyl‐3[4‐(methanesulfonyl)phenyl]‐2,3′‐bipyridine) is a highly active and selective cyclo‐oxygenase II inhibitor. A single, stability‐indicating HPLC method has been developed and validated for both the impurity and quantitative analysis of etoricoxib. Method development incorporated the optimization of stationary phase, pH, temperature, and mobile phase composition for the resolution of thirteen process impurities and three major degradation products. Further optimization of pH and mobile phase composition was aided by the use of DryLab^®, a computer‐based simulation program. The stability‐indicating capability of the method was proven through the identification of photolytic and oxidative decomposition products. Method validation produced excellent results for linearity, precision, limit of quantitation and limit of detection, specificity, accuracy, recovery, and robustness. The identities of etoricoxib decomposition products were confirmed by UV, LC/MS, and NMR spectra.

Keywords:

• Etoricoxib
• NSAID
• HPLC‐MS
• Validation
• Stability‐indicating

Acknowledgments

The authors would like to thank Dr. Ian Davies for supplying samples of etoricoxib and the N‐oxide analog. Additionally, thanks to Mr. Robert Reamer for his work on the NMR identification of the photodegradates.

Notes

^aSpin–spin coupling constants (J) are reported in hertz.

1. ¹H NMR (600.03 MHz, tfa‐d) δ10.65 (s, 1H), 9.79 (s, 1H), 9.54 (s, 1H), 9.50 (s, 1H), 9.29 (s, 1H), 9.17 (d, J = 8.6, 1H), 8.74 (d, J = 8.6, 1H), 3.50 (s, 3H), 3.23 (s, 3H).

2. ¹H NMR (600.03 MHz, tfa‐d) δ10.28 (d, J = 8.7, 1H), 9.99 (s, 1H), 9.61 (s, 1H), 9.41 (s, 1H), 9.28 (d, J = 8.7, 1H), 8.77 (d, J = 8.7, 1H), 8.42 (d, J = 8.7, 1H), 3.53 (s, 3H), 3.39 (s, 3H).