Rapid and sensitive determination of amoxicillin in human plasma by LC-MS/MS and the bioavailability of two amoxicillin capsules

doi:10.12092/j.issn.1009-2501.2018.01.014

Abstract

Abstract:

AIM: To establish a rapid and sensitive LC-MS/MS method for determination of amoxicillin in human plasma and to study the bioavailability of two amoxicillin capsules. METHODS: Shimadzu LCMS-8060 series LC-MS/MS was used. Amoxicillin（m/z 366.00/114.00）and d4-amoxicillin (internal standard, m/z 370.10/114.05) were monitored by ESI in MRM model. The analysts were eluted on Waters ACQUITY BEH C18 column ( 2.1×50 mm，1.7 μm) according to gradient elution program. The plasma samples were mixed with internal standard, then precipitated protein by methanol, the supernatants were detected. RESULTS: The linear, accuracy, precision, LLOQ, extraction recovery, specificity, matrix effect, stability of our method all met the guiding principles and criteria of CFDA. Compared with the literature reports, our method was simple, rapid, sensitive and had better chromatographic peaks. CONCLUSION: The method is rapid, sensitive and suitable for the determination of amoxicillin in human plasma. The test capsule is bioequivalence to the reference capsule.

Key words: amoxicillin, plasma concentration, LC-MS, bioequivalence, consistency evaluation

CLC Number:

R969.1

NAN Feng, XU Nan, CHEN Zhihui, XIANG Jin, LIANG Maozhi, TAO Zeting, YE Wei. Rapid and sensitive determination of amoxicillin in human plasma by LC-MS/MS and the bioavailability of two amoxicillin capsules[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(1): 73-77.

References

［1］CFDA.关于落实《国务院办公厅关于开展仿制药质量和疗效一致性评价的意见》有关事项的公告(2016年第106号)［EB/OL］.(2016-05-26)［2017-09-15］. http://www.sda.gov.cn/WS01/CL0087/154042.html.
［2］CFDA.化学药物制剂人体生物利用度和生物等效性研究技术指导原则［EB/OL］.(2005-03-18)［2017-09-15］. http://www.sda.gov.cn/WS01/CL1616/83421.html.
［3］沈铮,张亮,冯艳.HPLC-MS同时测定人血浆中阿莫西林和克拉维酸浓度［J］.中国药科大学学报, 2002,33(1):24-27.
［4］卢晓阳,申图建中,吴丽花,等.阿莫西林克拉维酸钾片的人体生物等效性研究［J］.中国药学杂志，2004,39(8):617-619。
［5］周伦,杨静,宋薇,等. 阿莫西林克拉维酸钾分散片的人体生物等效性研究［J］.中国新药杂志, 2014,23(21):2530-2535.
［6］高瞰, 刑俊家. LC/MS/MS法测定人血浆中阿莫西林克拉维酸浓度及其药物代谢动力学及人体生物等效性研究［J］.山西医药杂志, 2011,40(8):831-833.
［7］Reyns T, De Baere S, Croubels S, et al. Determination of clavulanic acid in calf plasma by liquid chromatography tandem mass spectrometry ［J］.J Mass Spectrom, 2006, 41(11): 1414-1420.
［8］Yoon KH, Lee SY, KIM W, et al. Simultaneous determination of amoxicillin and clavulanic acid in human plasma by HPLC-ESI mass spectrometry ［J］. J Chromatogr B, 2004, 813(1/2):121-127.
［9］魏敏吉,张慧琳,孙培红,等. 阿莫西林/克拉维酸两种口服制剂在健康人体的生物等效性研究［J］.中国临床药理学杂志, 2016,32(18):1684-1688.
［10］秦璐,皮佳鑫,祁东利,等. UPLC-MS/MS 测定阿莫西林脉冲片在犬体内的药动学和生物等效性［J］.天津医科大学学报, 2016,22(5):448-451.
［11］苗佳，南峰，沈奇，等.注射用阿莫西林钠克拉维酸钾(10∶1)临床药代动力学研究［J］. 四川大学学报（医学版）, 2013,44(2):246-250.

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