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

Abstract

FLZ 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 Chinese healthy volunteers after oral administration of FLZ tablets.

• Authors: Cheng Cui, Rui Chen, Ji Jiang, Rui Liu, Wei Wang, Qian Zhao, Pei Hu
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 164 Pg. 32-40 (Feb 05 2019) ISSN: 1873-264X [Electronic] England
• PMID: 30342394 (Publication Type: Journal Article, Validation Study)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Antiparkinson Agents
• Benzeneacetamides
• Phenols
• Tablets
• squamosamide

Topics

• Administration, Oral
• Antiparkinson Agents (administration & dosage, analysis, pharmacokinetics)
• Benzeneacetamides (administration & dosage, analysis, pharmacokinetics)
• Chromatography, High Pressure Liquid (instrumentation, methods)
• Healthy Volunteers
• Humans
• Male
• Phenols (administration & dosage, analysis, pharmacokinetics)
• Solid Phase Extraction (instrumentation, methods)
• Spectrometry, Mass, Electrospray Ionization
• Tablets
• Tandem Mass Spectrometry (instrumentation, methods)