Determination of betaxolol, a new beta-blocker, by gas chromatography mass spectrometry: Application to pharmacokinetic studies

Abstract

Betaxolol, a beta selective adrenoceptor antagonist recently approved for the treatment of hypertension, was determined by monitoring in chemical ionization mode with ammonia the [MH]⁺ ions of the trimethylsilyl derivatives of the drug and of its internal standard ((²H₅)betaxolol). Its pharmacokinetic profile obtained following administration of a 20 mg oral dose was characterized by a half‐life of 22 h and a bioavailability of 85%. The main acid metabolite formed by elimination of the isopropylamino group may also be determined as the methyl TMS derivative but methylation with BF₃‐methanol should be used with caution since it may induce the opening of the cyclopropyl group. The routine electron capture determination procedure was compared to this mass spectrometric method and an excellent correlation was found (r = 0.9974). Both procedures have the same sensitivity (1 ng ml⁻¹). Finally it was observed that under electron impact mode betaxolol trimethylsilyl side chain rearranged to lose TMSOCHCH₂; this elimination was confirmed by deuterium labelling studies.