Novel UHPLC-MS/MS method for the determination of rotigotine in the plasma of patients with Parkinson's disease

A novel ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of the dopamine receptor agonist rotigotine in human plasma. Following liquid-liquid extraction with tert-butyl methyl ether from 500 mu L plasma, the chromatographic analysis was performed on a Gemini NX3 column using 5mm pH 5.0 ammonium acetate-5mm ammonium acetate in methanol as binary gradient mobile phase, at a flow rate of 0.3 mL/min. The MS/MS ion transitions were 316.00 -> 147.00 for rotigotine and 256.10 -> 211.00 for the internal standard (lamotrigine). The lower limit of quantitation was 50 pg/mL and the linearity was determined from 50 to 2500 pg/mL. The mean recovery was 96.9%. Both intra-and interassay imprecision and inaccuracy were 15% at all quality control concentrations. The method was successfully applied to measure morning trough plasma rotigotine concentrations in a series of patients with Parkinson's disease on chronic treatment. The present study describes the first fully validated method for rotigotine determination in human plasma.