A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode. Methods: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 μL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm×2.1 mm i.d., 2.6-μm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode. Results: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R2>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance. Conclusions: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.
Abstract
Background: This study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode. Methods: Sarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 μL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm×2.1 mm i.d., 2.6-μm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode. Results: The developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R2>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance. Conclusions: A simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.
참고문헌 (11)
- Muntasir HA, "Inverse agonist activity of sarpogrelate, a selective 5-HT2A-receptor antagonist, at the constitutively active human 5-HT2A receptor", J Pharmacol Sci, 102, pp.189~195 (2006)
- Ogawa T, "Pharmacological profiles of R-96544, the active form of a novel 5-HT2A receptor antagonist R-102444", Eur J Pharmacol, 457, pp.107~114 (2002)
- Israilova M, "Binding and functional affinity of sarpogrelate, its metabolite m-1 and ketanserin for human recombinant alpha-1-adrenoceptor subtypes", Pharmacology, 65, pp.69~73 (2002)
- propoxybenzaldehyde-O-(substituted) benzyl oximes, "Arch Pharm (Weinheim)", 2007, 135~139
- Saini HK, "Therapeutic potentials of sarpogrelate in cardiovascular disease", Cardiovasc Drug Rev, 22, pp.27~54 (2004)
- Uchiyama S, "Effect of sarpogrelate, a 5-HT(2A) antagonist, on platelet aggregation in patients with ischemic stroke: clinical-pharmacological dose-response study", Cerebrovasc Dis, 24, pp.264~270 (2007)
- Patankar S, "Rapid and sensitive LC−MS–MS method for the determination of sarpogrelate in human plasma", Chromatographia, 69, pp.671~676 (2009)
- Nirogi R, "Liquid chromatography tandem mass spectrometry method for the quantification of sarpogrelate, a selective 5-HT2A receptor antagonist, in plasma: application to a pre-clinical pharmacokinetic study", Biomed Chromatogr, 24, pp.1159~1167 (2010)
- Zhang C, "Validated LC-MS", MS method for the determination of sarpogrelate in human plasma: application to a pharmacokinetic and bioequivalence study in Chinese volunteers, 2010, pp.53, 546~551
- Kim TE, "Comparison of pharmacokinetics between sarpogrelate hydrochloride immediate-release formulation and controlled-release formulation", Int J Clin Pharmacol Ther, 51, pp.114~119 (2013)
- "Guidance for industry: Bioanalytical method validation" (2013)[URL]