Simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate in rat plasma by high-performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study

A sensitive, simple and rapid HPLC-MS/MS method has been developed and validated for the simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate (AEPD) in rat plasma in the present study The analytes were separated on a C(18) column (5 mu m, 2.1 mm x 150 mm) with a security guard C18 column (5 mu m, 4 mm x 20 mm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. With alpha-methyldopa as internal standard, sample pretreatment involved in a one-step protein precipitation with 0.4 M perchloric acid. The method was linear over the concentration ranges of 50-5000 ng/ml for L-dopa and 12 5-2500 ng/ml for AEPD. The ultra-day and inter-day relative standard deviations (RSD) were less than 15% and the relative errors (RE) were all within 15%. Finally, the method was successfully applied to support the pharmacokinetic study after L-dopa and its prodrug AEPD were orally administrated to the Sprague-Dawley rats, respectively (C) 2010 Elsevier B.V. All rights reserved