Determination of zofenopril and its active metabolite in human plasma using high-performance liquid chromatography combined with a triple-quadruple tandem mass spectrometer

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Abstract

A simple, selective and sensitive LC-MS-MS method has been developed and validated to simultaneously quantify zofenopril and its active metabolite zofenoprilat in human plasma, using diazepam as internal standard. 1,4-Dithiothreitol was used as a reducer to release and stabilize the thiol group of zofenoprilat from dimer and mixed forms with endogenous thiols in the treatment of plasma samples. After a liquid-liquid extraction with methyl tert-butyl ether under acidic conditions, the post-treatment samples were analyzed on an Agilent ZORBAX Eclipse XDB-C8 column interfaced with a triple-quadruple tandem mass spectrometer using positive electrospray ionization. A solution of methanol and 0.1% formic acid solution (85:15, v/v) was used as the isocratic mobile phase with a flow rate of 0.2 mL/min. The method was validated to demonstrate the specificity, lower limit of quantitation, accuracy and precision of measurements. The validated LC-MS-MS method has been successfully applied to study the pharmacokinetics of zofenopril calcium in healthy Chinese volunteers.

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Tian, Y., Cao, J., Luo, L., Zhang, Z., & Ma, P. (2015). Determination of zofenopril and its active metabolite in human plasma using high-performance liquid chromatography combined with a triple-quadruple tandem mass spectrometer. Journal of Chromatographic Science, 53(2), 253–262. https://doi.org/10.1093/chromsci/bmu050

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