Analytical Sciences

Rapid and Simultaneous Quantitation of Amoxicillin and Clavulanic Acid in Human Plasma and Urine by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

Yaxin FAN,*,** Xiaojie WU,*,** Miao ZHAO,*,** Beining GUO,*,** Guoying CAO,*,** Jicheng YU,*,** Yuancheng CHEN,*,** and Jing ZHANG*,**

*Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai 200040, China
**Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, 12 Wulumuqi Zhong Rd, Shanghai 200040, China

Rapid, accurate and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for the simultaneous quantitation of amoxicillin and clavulanic acid in human plasma and urine samples. Amoxicillin and clavulanic acid in both plasma and urine were extracted using a solid-phase extraction method. The compounds were separated on an Acquity UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm). Ampicillin was used as the internal standard (IS) in plasma, while amoxicillin-d₄ and sulbactam were used as ISs in urine. The lower limit of quantitation was 0.0500 and 0.0250 μg/mL for amoxicillin and clavulanic acid in plasma, and 0.0500 μg/mL for both analytes in urine. The established methods were validated in terms of selectivity, precision, accuracy, linearity, matrix effect, recovery, carryover, interaction, dilution integrity and stability, and successfully applied to a pharmacokinetic study of amoxicillin sodium and clavulanate potassium (10:1) injection in healthy volunteers.

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