Accurate analysis of ginkgolides and their hydrolyzed metabolites by analytical supercritical fluid chromatography hybrid tandem mass spectrometry.
Hydrolysis plays an important role in the metabolic transformations of lactones. Analysis of lactones and their hydrolyzed metabolites in biological samples is challenging, because unexpected hydrolysis or reversed dehydration may occur depending on the test environments. In this work, a supercritical fluid chromatography hybrid triple-quadrupole mass spectrometry (SFC-QQQ MS) method has been proposed for simultaneous analysis of ginkgolides and hydrolyzed metabolites. The SFC utilizes carbon dioxide as the mobile phase, avoiding hydrolysis of ginkgolides that always happens during reversed phase liquid chromatographic detection. Compared with normal phase liquid chromatography, the SFC provides good resolutions especially for ginkgolide with similar structures. This SFC-QQQ MS method was validated in linearity, precision, accuracy, and stability for ginkgolides and metabolites. Then this method was successfully applied to pharmacokinetic study of 3 ginkgolides and their 6 hydrolyzed metabolites after intravenous administration of total ginkgolide extract. Ginkgolides and metabolites showed different clear rates and excluded in 2-4h. The developed SFC-QQQ MS method allows accurate determination of ginkgolides and metabolites with high resolutions, and can be extended to analysis of other water-unstable compounds.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Xin-Guang
XG
Liu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Lian-Wen
LW
Qi
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Zhi-Ying
ZY
Fan
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Xin
X
Dong
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Ru-Zhou
RZ
Guo
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Feng-Chang
FC
Lou
Area della Ricerca di Roma I, Istituto di Metodologie Chimiche, CNR, I-00015 Monterotondo Scalo, Italy.
Salvatore
S
Fanali
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
Ping
P
Li
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 104yang104@163.com.
Hua
H
Yang
D002853:Chromatography, Liquid / Q000379:methods*; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D046934:Ginkgolides / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D046934:Ginkgolides
Ginkgo; Ginkgolides; Hydrolyzed metabolites; Pharmacokinetics; Supercritical fluid chromatography hybrid tandem mass spectrometry