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A specific, accurate, precise and reproducible high‐performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous quantitation of five 3‐hydroxy‐3‐methyglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, viz. atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin, in pharmaceutical formulations and extended the application to in vitro metabolism studies of these statins. Ternary gradient elution at a flow rate of 1 mL/min was employed on an Intertisl ODS 3V column (4.6 × 250 mm, 5 µm) at ambient temperature. The mobile phase consisted of 0.01 m ammonium acetate (pH 5.0), acetonitrile and methanol. Theophylline was used as an internal standard (IS). The HMG‐CoA reductase inhibitors and their metabolites were monitored at a wavelength of 237 nm. Drugs were found to be 89.6–105.6% of their label's claim in the pharmaceutical formulations. For in vitro …