Development of a UPLC-MS/MS method to determine metoprolol content in human plasma and its application in bioequivalence study

YANG Huan; LI Chao; TANG Zhi

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (2) : 130-135.

Development of a UPLC-MS/MS method to determine metoprolol content in human plasma and its application in bioequivalence study

YANG Huan¹, LI Chao², TANG Zhi²

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Abstract

Objective Establishment of a UPLC-MS/MS method to determine the concentration of metoprolol in human plasma for human bioequivalence study. Methods Plasma samples were prepared by protein precipitation method, and with metoprolol-d6 as the internal standard. The chromatographic column was waters ACQUITY UPLC BEH C18 1.7 μm (2.1×50 mm), 0.1% formic acid solution (solution A) as mobile phase-A, acetonitrile (solution B) as mobile phase-B; the gradient elution conditions were 20% solution B at 0-0.2 min, 20%-90% solution B at 0.2-1.2 min, 90% solution B at 1.2-1.5 min, 90%-20% solution B at 1.5-2.0 min, with a flow rate of 0.4 mL·min^-1 and column temperature of 40℃. Electrospray ion source was detected by the positive ion scanning with multiple reaction monitoring mode. The ion pairs of metoprolol and the internal standard metoprolol-d6 were m/z 268.04 → m/z115.77 and m/z 274.04 → m/z 121.83 respectively. Results The determination of the substances to be measured was not interfered by the endogenous substances in the plasma, and the quantitative range of metoprolol in human plasma was 0.500-50.000 ng·mL^-1with good linearity (R²=0.999 683). The recovery of metoprolol was 96.87%-97.96%, without obvious matrix effect. The intra- and inter-batch accuracy and precision all met requirement. Conclusion The method is accurate and stable. The sample pretreatment and injection is simple and fast, meeting the quantitative analysis of human bioequivalence study of metoprolol.

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metoprolol / bioequivalence / ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)

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YANG Huan, LI Chao, TANG Zhi. Development of a UPLC-MS/MS method to determine metoprolol content in human plasma and its application in bioequivalence study[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(2): 130-135

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