AT1 receptor blockers are agents for the treatment of hypertension. Rapid and precise assay methods are needed to evaluate possible sub- or overdosage. A direct on-line solid phase extraction coupled to tandem mass spectrometry was developed and validated to determine valsartan (5-2000ng/mL) or candesartan (1-200ng/mL) in human plasma and urines. Both intra- and inter-assay accuracy and precision were in the range 89.2-111% and 0.9-16.9% RSD. Total run time was 4.5min. This on-line clean-up-MS method was found to be robust for the analysis of a high number of samples with unvarying performance.