Quantitative determination of atorvastatin and ortho-hydroxy atorvastatin in human plasma by liquid chromatography tandem mass spectrometry and pharmacokinetic evaluation.
A specific, sensitive and simple method was developed to determine the levels of both atorvastatin and ortho-hydroxy atorvastatin in human plasma. The analytes and internal standard pitavastatin were extracted from plasma by liquid-liquid extraction, separated on a Zorbax SB-C18 column, eluted with a mobile phase of water:acetonitrile (45:55 v/v), both containing 5% methanol and 0.01% formic acid. Detection was performed with an electrospray ionization triple quadrupole mass spectrometer in positive ion mode using multiple reaction monitoring. The standard calibration curves of atorvastatin and ortho-hydroxy atorvastatin were linear in the concentration range of 0.2-20 and 0.1-20 ng/mL, respectively. The intra- and inter-day precisions were < 7.7% and the accuracy was within ± 5.9%. The method has been successfully used for the study of the pharmacokinetics of atorvastatin and ortho-hydroxy atorvastatin in Chinese patients with coronary heart disease after a single oral dose of 20 mg atorvastatin. The mean values for the area under the plasma concentration-time curve for atorvastatin and ortho-hydroxy atorvastatin were 63.1 and 46.9 ng.h/mL, respectively.
Department of Pharmacology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, PR China. gzzsjzhs@163.com
B X
BX
He
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L
Shi
J
J
Qiu
X H
XH
Zeng
L
L
Tao
R
R
Li
C J
CJ
Hong
X L
XL
Gu
F Y
FY
Dong
L
L
Yang
S J
SJ
Zhao
D019540:Area Under Curve; D000069059:Atorvastatin / Q000031:analogs & derivatives; D002851:Chromatography, High Pressure Liquid; D006538:Heptanoic Acids / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D011758:Pyrroles / Q000097:blood / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013997:Time Factors
C518963:2-hydroxyatorvastatin; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin