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J Pharm Biomed Anal. 2018 Jul 15;156:199-205. doi: 10.1016/j.jpba.2018.04.010. Epub 2018 Apr 14.

Simultaneous determination of Pyragrel, a novel anti-thrombotic agent, and its two primary metabolites in plasma by HPLC-MS/MS.

Author information

1
Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
2
Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
3
Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China; Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China. Electronic address: thy_2012@126.com.
4
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. Electronic address: liu3xo@ucmail.uc.edu.

Abstract

Pyragrel is a novel thromboxane A2-synthetase inhibitor for the treatment of cerebral infarction, and it is currently being investigated in phase I clinical trials. This paper reports the first reliable LC-MS/MS method for the simultaneous determination of Pyragrel and its two main metabolites, M1 and M2, in human plasma. All analytes were extracted from human serum using liquid-phase extraction and separated on a Zorbax EcLipse XDB C18 column using isocratic elution with a mobile phase composed of methanol, water and formic acid (65:35:0.1, v/v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring transitions under positive electrospray ionization were performed at m/z 329.0 → m/z 135.9 for Pyragrel, m/z 303.1 → m/z 135.0 for M1, m/z 331.2 → m/z 135.0 for M2, and 482.2 → m/z 258.0 for IS, respectively. The following parameters were validated: specificity, recovery, matrix effects, carry-over, linearity, sample stability under a variety of storage and handling conditions, and stock solution stability. The validated method has been successfully applied to an initial pharmacokinetic study in healthy volunteers following intravenous administrations of 60 mg of Pyragrel, and this method will facilitate further studies involving more comprehensive identification of the metabolic profile of Pyragrel and the appropriate dosage regimen.

KEYWORDS:

Human plasma; LC–MS/MS; Pharmacokinetics; Pyragrel

PMID:
29727781
DOI:
10.1016/j.jpba.2018.04.010
[Indexed for MEDLINE]

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