Sensitive liquid chromatography-tandem mass spectrometry method for the determination of loratadine and its major active metabolite descarboethoxyloratadine in human plasma

A sensitive method for the simultaneous determination of loratadine and its major active metabolite descarboethoxyloratadine (DCL) in plasma was devel oped, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. The samples were extracted from plasma with t oluene followed by back-extraction into formic acid (2%) for DCL after whic h the toluene containing the loratadine was evaporated, the analyte reconst ituted and combined with the DCL back-extract. Chromatography was performed on a Phenomenex Luna C-18 (2) 5-mum, 150X2.1-mm column with a mobile phase consisting of acetonitrile-0.1% formic acid using gradient elution (10 to 90% acetonitrile in 2 min) at a flow-rate of 0.3 ml/min. Detection was achi eved by a Perkin-Elmer API 2000 mass spectrometer (LC-MS-MS) set at unit re solution in the multiple reaction monitoring mode. TurboIonSpray ionisation was used for ion production. The mean recovery for loratadine and descarbo ethoxyloratadine was 61 and 100%, respectively, with a lower limit of quant ification at 0.10 ng/ml for both the analyte and its metabolite. This is th e fist assay method described for the simultaneous determination of loratad ine and descarboethoxyloratadine in plasma using one chromatographic run. T he method is sensitive and reproducible enough to be used in pharmacokineti c studies. (C) 2001 Published by Elsevier Science BN.