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采用亲水作用液相色谱-电喷雾串联质谱法测定法医全血样本中的二甲双胍及其他双胍类药物。

Determination of metformin and other biguanides in forensic whole blood samples by hydrophilic interaction liquid chromatography-electrospray tandem mass spectrometry.

作者信息

Sørensen Lambert K

机构信息

Section for Toxicology and Drug Analysis, Department of Forensic Medicine, Aarhus University, Brendstrupgaardsvej 100, Aarhus N, Denmark.

出版信息

Biomed Chromatogr. 2012 Jan;26(1):1-5. doi: 10.1002/bmc.1615. Epub 2011 Mar 4.

DOI:10.1002/bmc.1615
PMID:21374650
Abstract

Metformin is an anti-diabetic drug in the biguanide class which also includes phenformin and buformin. Because of the potential adverse effects of the biguanides, a reliable liquid chromatography-tandem mass spectrometry method using pneumatically assisted electrospray ionization was developed for the quantification of the drugs in both live and post-mortem human whole blood. The blood proteins were precipitated by the addition of a mixture of methanol and acetonitrile, and the extract was cleaned up by cation-exchange solid-phase extraction to eliminate ion suppression effects. The separation was performed by hydrophilic interaction liquid chromatography. Matrix-matched calibrants combined with isotope dilution of metformin were used for calibration. The detection limits were 0.01 mg/L for metformin and phenformin and the relative intra-laboratory reproducibility standard deviations were less than 6% at concentrations of 1-10 mg/L. The mean true recoveries were greater than 86%.

摘要

二甲双胍是双胍类抗糖尿病药物,该类还包括苯乙双胍和丁双胍。由于双胍类药物存在潜在不良反应,因此开发了一种可靠的液相色谱-串联质谱法,该方法采用气动辅助电喷雾电离技术,用于定量生前和死后人体全血中的这些药物。通过添加甲醇和乙腈的混合物使血液蛋白沉淀,提取物通过阳离子交换固相萃取进行净化,以消除离子抑制效应。采用亲水相互作用液相色谱进行分离。使用与二甲双胍同位素稀释相结合的基质匹配校准物进行校准。二甲双胍和苯乙双胍的检测限为0.01 mg/L,在1-10 mg/L浓度下,实验室内相对重现性标准偏差小于6%。平均真实回收率大于86%。

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Therapeutic Concentrations of Metformin: A Systematic Review.二甲双胍的治疗浓度:一项系统评价
Clin Pharmacokinet. 2016 Apr;55(4):439-59. doi: 10.1007/s40262-015-0323-x.