Simultaneous determination of FLZ and its metabolite (M1) in human plasma and urine by UHPLC-MS/MS: Application to a pharmacokinetic study

Publication date: Available online 10 October 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Cheng Cui, Rui Chen, Ji Jiang, Rui Liu, Wei Wang, Qian Zhao, Pei HuAbstractFLZ is a novel anti-Parkinson’s disease candidate drug. The main active metabolite is FLZ O-dealkylation (M1) in preclinical studies. A reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) quantitation method was developed for the simultaneous determination of FLZ and M1 with low limits of quantitation in human plasma (0.1 ng/mL) and urine (0.5 ng/mL). The plasma and urine samples were both purified by full-automatic solid phase extraction (SPE) method with ensured high extraction recovery and little matrix effect for both analytes, and then separated on a BEH C18 column (2.1 × 50 mm, 1.7 μm). Detection and quantification were performed using an electrospray ionization (ESI) source in positive mode by multiple reaction monitoring (MRM). The precursor to product ion transitions were monitored at m/z 450.3+→313.2+ for FLZ, m/z 436.3+→299.1+ for M1, m/z 462.6+→142.0+ for [D12]-FLZ (internal standard of FLZ) and m/z 447.2+→125.2+ for [D11]-M1 (internal standard of M1), respectively. This method showed good linearity, accuracy, precision and stability in the range of 0.1-100 ng/mL in plasma and 0.5-500 ng/mL in urine of two analytes. Finally, the developed method was successfully applied to a pharmacokinetic research in Chin...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research