Quantitative analysis of racecadotril metabolite in human plasma using a liquid chromatography/tandem mass spectrometry.
Orally administered racecadotril is rapidly hydrolyzed to the more potent enkephalinase inhibitor thiorphan in vivo. A sensitive and specific liquid chromatography/tandem mass spectrometry method was developed and validated to quantify thiorphan in human plasma using lisinopril as the internal standard. After a simple protein precipitation with methanol, the post-treatment samples were analyzed on a CN column interfaced with a triple-quadruple tandem mass spectrometer using negative electrospray ionization. The method was validated to demonstrate the specificity, lower limit of quantification, accuracy, and precision of measurements. The assay was linear over the concentration range 9.38-600 ng/mL using a 5 microL aliquot of plasma. The correlation coefficients for the calibration curves ranged from 0.9985 to 0.9995. The intra- and inter-day precisions over the entire concentration were not more than 6.33%. Methanol and water (35:65, v/v) is used as the isocratic mobile phase, with 0.1% of formic acid in water. The method was successfully applied for pharmacokinetic study after a single oral administration of 200 mg racecadotril to 20 healthy volunteers.
Xu
Yu
Y
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China. xyu@ustc.edu.cn
Huang
Jinchang
J
Liu
Fei
F
Gao
Shu
S
Guo
Qingxiang
Q
D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
C049331:racecadotril; D015244:Thiorphan; D015260:Neprilysin