An improved LC-MS/MS method for quantitative determination of ilaprazole and its metabolites in human plasma and its application to a pharmacokinetic study.
OBJECTIVE
To improve and validate an analytical method based on liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the quantitative measurement of ilaprazole and its two metablites in human plasma.


METHODS
Separation of analytes and the internal standard (IS), omeprazole, was performed on a Thermo HyPURITY C18 column (150x2.1 mm, 5 microm) with a mobile phase consisting of 10 mmol/L ammonium formate water-acetonitrile solution (50:50, v/v) at a flow rate of 0.25 mL/min. The API4000 triple quadruple mass spectrometer was operated in multiple reactions monitoring mode via positive electrospray ionization interface using the transition m/z 367.2 --> m/z184.0 for ilaprazole, m/z 383.3 --> m/z 184.1 for ilaprazole sulfone, m/z 351.2 --> m/z 168.1 for ilaprazole thiol ether and m/z 346.2 --> m/z 198.0 for omeprazole.


RESULTS
The method was linear over the concentration range of 0.23-2400.00 ng/mL for ilaprazole, 0.05-105.00 ng/mL for ilaprazole thiol ether and 0.06-45.00 ng/mL for ilaprazole sulfone. The intra- and inter-day precisions were all less than 15% in terms of relative standard deviation (RSD), and the accuracy was within 15% in terms of relative error (RE) for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether. The lower limit of quantification (LLOQ) was identifiable and reproducible at 0.23, 0.05 and 0.06 ng/mL with acceptable precision and accuracy for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether, respectively.


CONCLUSIONS
The validated method offered sensitivity and a wide linear concentration range. This method was successfully applied for the evaluation of the pharmacokinetics of ilaprazole and its two metabolites after single oral doses of 5 mg ilaprazole to 12 healthy Chinese volunteers.
Zhou
Gan
G
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
Tan
Zhi-rong
ZR
Zhang
Wei
W
Ou-Yang
Dong-sheng
DS
Chen
Yao
Y
Guo
Dong
D
Liu
Ying-zi
YZ
Fan
Lan
L
Deng
Han-wu
HW
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D001562:Benzimidazoles / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013450:Sulfones / Q000097:blood* / Q000493:pharmacokinetics; D013454:Sulfoxides / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D013450:Sulfones; D013454:Sulfoxides; C574790:ilaprazole sulfone; C119615:ilaprazole
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