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 C18 column (150 mm × 4.5 mm i.d.) and acetonitrile/0.05% phosphoric acid (35:65) at pH 2.6. The method could determine (I) in the range of 0.3– 28 (mu)g ml^-1 with mean percentage recovery of 100.29 (plus-minus) 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 (I) in presence of (II), (III) and (IV) with linearity range of 2–36 (mu)g ml^-1 and with mean percentage recovery of 99.53 (plus-minus) 1.613 and 99.31 (plus-minus) 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 t1/2 =13.5 min using 0.051 M sodium hydroxide at 25 °C, other kinetic data were also presented. The three methods were applied to the analysis of pharmaceutical dosage forms and bulk powder.