Determination of acidic and neutral therapeutic drugs in human blood by liquid chromatography-electrospray tandem mass spectrometry

A liquid chromatography-tandem mass spectrometry method using pneumatically assisted electrospray ionisation (LC-ESI-MS/MS) was developed for the simultaneous determination of paracetamol, naproxen, ibuprofen, etodolac, diclofenac, salicylic acid, lamotrigine, carbamazepine, 10-OH-carbazepine, phenytoin, phenobarbital, barbital, cyclobarbital, pentobarbital, amobarbital and caffeine in human live and post-mortem whole blood. The blood proteins were precipitated in a mixture of methanol and acetonitrile, and the extract was purified by ultrafiltration. The separation was performed on an ether-linked phenyl column with polar endcapping, and both negative and positive ESI were applied. Matrix-matched standards were used for calibration. The relative intra-laboratory reproducibility standard deviations were, in general, better than 8% at concentrations in the therapeutic range. The mean true recoveries were in the range 92-101% for the live blood and 84-101% for the post-mortem blood. (C) 2010 Elsevier Ireland Ltd. All rights reserved.