A HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD FOR THE SIMULTANEOUSDETERMINATION OF VENLAFAXINE AND O-DESMETHYLVENLAFAXINE IN BIOLOGICAL-FLUIDS

A rapid, accurate, and sensitive high-performance liquid chromato-grap hic (HPLC) method for simultaneous determination of venlafaxine (V) an d O-desmethylvenlafaxine (ODV) in plasma and urine has been developed. V and ODV are extracted from plasma using a liquid-liquid extraction procedure, chromatographed on a Supelcosil LC-8DB column, and quantita ted by UV detection at 229 nm. Linearity was established over the rang e 10-500 ng/ml for V and 7.2-720 ng/ml for ODV using 1.0 ml of human, rat, dog, and mouse plasma. For urine, for both analytes, an analytica l range 0.1-10.0 mu g/ml was established. Accuracy of >+/-10% about th e theoretical mean was achieved for all matrices, with intra- and inte rday coefficients of variation for precision of <10%. Endogenous compo nents in plasma and/or urine or known metabolites of V do not interfer e in the determination of the analytes. For both V and ODV a quantitat ion limit of 10 ng/ml for plasma was adequate for their estimation ove r a period of three half-lives, following administration of a pharmaco logic dose in man, and the limit of 0.1 mu g/ml, for urine, can monito r excretion of as little as 0.5% of the dose.