Micro liquid chromatographic assay for the determination of plasma-unbound atenolol

An improved high performance liquid chromatographic assay for plasma-unbound atenolol is described. The assay has a wide range (10-5000 ng ml(-1)) of linearity and a detection limit of 5 ng ml(-1) (or 0.1 ng per injection) with acceptable intra- and inter-assay reproducibilities using small volumes of plasma (100 mu l). Following administration of a single dose of atenolol to the rat, nine blood samples were collected over a period of 8 h. These samples were analyzed for atenolol concentrations by a sensitive and specific microbore high performance liquid chromatograph with a photodiode-array detector. This multi-channel detector was used to acquire spectral information on atenolol and demonstrated a superior performance in comparison to all other techniques in that both qualitative and quantitative information were acquired with the system. Because of it sensitivity and applicability to plasma analysis, the assay can be used for pharmacokinetic studies and is valuable in therapeutic drug monitoring.