Profiling and Preparation of Metabolites from Pyragrel in Human Urine by Online Solid-Phase Extraction Coupled with High Performance Liquid Chromatography Tandem Mass Spectrometry Followed by a Macroporous Resin-Based PurificationReport as inadecuate


Profiling and Preparation of Metabolites from Pyragrel in Human Urine by Online Solid-Phase Extraction Coupled with High Performance Liquid Chromatography Tandem Mass Spectrometry Followed by a Macroporous Resin-Based Purification


Profiling and Preparation of Metabolites from Pyragrel in Human Urine by Online Solid-Phase Extraction Coupled with High Performance Liquid Chromatography Tandem Mass Spectrometry Followed by a Macroporous Resin-Based Purification - Download this document for free, or read online. Document in PDF available to download.

1

Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

2

Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

3

Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China

4

Hefei Institute of Pharmaceutical Industry Co., Ltd., Wenshan Road, Hefei 230601, China

5

Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100 Haining Road, Shanghai 200080, China

6

Laboratory of Drug Metabolism & Pharmacokinetics, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China





*

Authors to whom correspondence should be addressed.



Abstract Pyragrel, a new anticoagulant drug, is derived from the molecular combination of ligustrazine and ferulic acid. Pyragrel showed significant inhibitory activity against platelet aggregation induced by adenosine diphosphate ADP, and had been approved for a phase I clinical trial by CFDA. To characterize the metabolites of Pyragrel in human urine after intravenous administration, a reliable online solid-phase extraction couple with high performance liquid chromatography tandem mass spectrometry online SPE-HPLC-MSn method was conceived and applied. Five metabolites were detected and tentatively identified, which suggested that the major metabolic pathways of Pyragrel in human were double-bond reduction, double-bond oxidation, and then followed by glucuronide conjugation. Two main metabolites were then prepared using β-glucuronide hydrolysis and macroporous resin purification approach followed by preparative high-performance liquid chromatography PHPLC method, with their structures confirmed on the basis of nuclear magnetic resonance NMR data. This study provided information for the further study of the metabolism and excretion of Pyragrel. View Full-Text

Keywords: Pyragrel; metabolite; human urine; online SPE-HPLC-MSn; macroporous resin; PHPLC Pyragrel; metabolite; human urine; online SPE-HPLC-MSn; macroporous resin; PHPLC





Author: Xin Zhao 1, Jingjing Jiang 2, Guang Yang 2, Jie Huang 3, Guoping Yang 3, Guangwei He 4, Zhaoxing Chu 4, Taijun Hang 1,* and Guorong Fan 2,5,6,*

Source: http://mdpi.com/



DOWNLOAD PDF




Related documents