Analysis of a basic drug by on‐line solid‐phase extraction liquid chromatography/tandem mass spectrometry using a mixed mode sorbent

Two on‐line configurations using multiple 6‐ and 10‐port valves were investigated for high‐flow on‐line extraction of a basic drug in rat plasma and human urine using a reversed‐phase and a cation‐exchange SPE sorbent. The first configuration studied was a single reversed‐phase extraction cartridge (2.1 × 20 mm, 25µm) using an optimized washing protocol. The results showed that up to 1.5 mL of sample (urine or plasma diluted 1:1) can be injected with limits of quantification (LOQs) as low as 100 pg/mL. The second configuration studied was the combination of a cation exchanger and a reversed‐phase cartridge using at‐column dilution. The results showed better LOQs than those obtained with the single cartridge at 10 pg/mL with the same injection volume. The mass spectrometer was operated in the multiple reaction monitoring (MRM) mode. All calibration curves gave an average of 5% relative standard deviation (RSD). Copyright © 2002 John Wiley & Sons, Ltd.