Determination of bupropion and its main metabolite in rat plasma by LC-MS and its application to pharmacokinetics.

A sensitive and selective liquid chromatograpy-mass spectrometry method for the determination of bupropion and its main metabolite, hydroxubupropion, in rat plasma was developed and validated. After addition of carbamazepine as internal standard (IS) and precipitation of protein with acetonitrile, the plasma samples were analyzed on an Agilent Zorbax SB-C18 (2.1 mm x 50 mm, 3.5 microm) column at 30 degrees C, with acetonitrile-0.1% formic acid as mobile phase at a flow rate of 0.4 mL min(-1). The detection was carried out in the selective ion monitoring mode with a positive electrospray ionization interface. The calibration curve was linear over the 10-2000 ng mL(-1) for bupropion and 5-1000 ng mL(-1) for hydroxybupropion in plasma. RSD of inter-day and intra-day precision was less than 7% for bupropion, 9% for hydroxybupropion. The developed method was successfully applied to pharmacokinetic studies after single intragastric administration of bupropion 15 mg kg(-1) to rats.