Liquid chromatography and chemometric methods for determination of rofecoxib in presence of its photodegradate and alkaline degradation products

Rofecoxib (I) has been determined in presence of its photodegradate (II) and alkaline degradation products (III) and (IV) by liquid chromatography method using a Shimpak ODS C-18 column (150mm x 4.5mm i.d.) and acetonitrile/0.05% phosphoric acid (35:65) at pH 2.6. The method could determine (1) in the range of 0.3-28 mug ml(-1) with mean percentage recovery of 100.29 +/- 0.979%. Also, two chemometric methods were developed using partial least square (PLS) and concentration residual augmented classical least square method (CRACLS). The methods could determine (1) in presence of (II), (III) and (IV) with linearity range of 2-36 mug ml(-1) and with mean percentage recovery of 99.53 +/- 1.613 and 99.31 +/- 1.42% for PLS and CRACLS, respectively. The PLS method was used to carry out a kinetic study of the alkaline degradation. The reaction rate constant was found to be k = 0.051 min(-1) and the t(1/2) =13.5 min using 0.051 M sodium hydroxide at 25 degreesC, other kinetic data were also presented. The three methods were applied to the analysis of pharmaceutical dosage forms and bulk powder. (C) 2004 Elsevier B.V. All rights reserved.