Rapid screening for 61 central nervous system drugs in plasma using weak cation exchange solid-phase extraction and high performance liquid chromatography with diode array detection

Rapid and accurate screening for toxicants/chemicals in a broad range is an important element in systematic toxicological analysis (STA). Herein, we report a novel method for the rapid screening of 61 central nervous system (CNS) drugs in plasma, using a solid-phase extraction (SPE) column termed, weak cation exchange (WCX) and high performance liquid chromatography with a diode array detector (HPLC-DAD). The SPE column was preconditioned sequentially with 3 ml of acetonitrile, 1 ml of water and, 2 ml of buffer solution. The pretreated plasma was loaded onto the column, which was then washed with 2 ml of water, followed by 2 ml of acetonitrile, and the acetonitrile elution was collected as the neutral/acid fraction. Subsequently, 3 ml of trifluoroacetic acid-acetonitrile (2+98) was then used to elute the column and the elution was collected as basic fraction. The collected fractions were evaporated at 60°C under a nitrogen stream until about 100 μl of solvent remained. The final volume was then adjusted to 1 ml with 5% of acetonitrile. The HPLC separation was accomplished on an Agilent TC-C18 column (250 × 4.6 mm, 5 µm) with acetonitrile and phosphate buffer solution as mobile phase, by gradient elution at a flow rate of 1.5 ml/min. The detection wavelength was 210 nm, and the full spectra were recorded from 200 to 364 nm. The absolute recoveries of 55 drugs tested, exceeded 50%; 42 of them exceeded 80%. In conclusion, the WCX SPE preparation combined with HPLC-DAD, is suitable for a broad drug screening for CNS drugs.   Key words: Solid phase extraction (SPE), weak cation exchange (WCX), high performance liquid chromatography with diode array detection (HPLC-DAD), systematic toxicological analysis (STA), drug screening.