Development of a new GC-MS/MS method for the determination of metformin in human hair.,Drug Testing and Analysis

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Development of a new GC-MS/MS method for the determination of metformin in human hair.
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2020-06-28 , DOI: 10.1002/dta.2866
Nadia Arbouche ₁ , Marie-Odile Batt ₂ , Jean-Sebastien Raul ₁ , Pascal Kintz _{1,

3}

Affiliation

Diabetes mellitus is one of the most important public health challenges. Metformin (1,1‐dimethylbiguanide) represents the “gold standard” for the treatment of diabetes mellitus type 2. Despite its important role in reducing mortality and morbidity in the diabetic population, metformin is associated with an increased risk of stroke. To document exposure to a drug, hair is considered to be the specimen of choice to complement blood and urine, since it provides historical detail of a subject's chronic exposure to drug(s). Measuring hair concentration of metformin can be important for forensic toxicologists investigating criminal poisoning or Munchausen's syndrome by proxy. In clinical toxicology, drug monitoring using hair to document metformin observance has not yet been described. To document the interest of hair analysis for metformin, the authors have developed and validated a method using a gas‐chromatography tandem mass spectrometry system and applied it to authentic hair obtained from 9 diabetic patients under daily treatment. The validation procedure demonstrated a LOD an LOQ of 1 and 100 pg/mg, respectively and acceptable linearity, repeatability and reproducibility. The hair of the 9 patients tested positive in the low ng/mg range with concentrations ranging from 0.3 to 3.8 ng/mg. It seems obvious, in comparison with other drugs, that metformin is badly incorporated into hair, as the daily dosage varied from 1 to 3 g. Although limited in the number of subjects, the study allowed to postulate a possible correlation between daily dose and concentration in dark hair, while for light hair no correlation was found.

中文翻译：

开发用于测定人头发中二甲双胍的新 GC-MS/MS 方法。

糖尿病是最重要的公共卫生挑战之一。二甲双胍（1,1-二甲基双胍）代表了治疗 2 型糖尿病的“金标准”。尽管二甲双胍在降低糖尿病人群的死亡率和发病率方面具有重要作用，但二甲双胍与卒中风险增加有关。为了记录药物暴露，头发被认为是补充血液和尿液的首选标本，因为它提供了受试者长期暴露于药物的历史细节。测量二甲双胍的头发浓度对于法医毒理学家通过代理调查犯罪中毒或孟乔森综合征非常重要。在临床毒理学中，尚未描述使用毛发来记录二甲双胍遵守情况的药物监测。为了记录头发分析对二甲双胍的兴趣，作者开发并验证了一种使用气相色谱串联质谱系统的方法，并将其应用于 9 名糖尿病患者日常治疗的真发。验证程序证明 LOD 和 LOQ 分别为 1 和 100 pg/mg，线性、重复性和再现性可接受。9 名患者的头发在低 ng/mg 范围内呈阳性，浓度范围为 0.3 至 3.8 ng/mg。很明显，与其他药物相比，二甲双胍在头发中的吸收很差，因为每日剂量从 1 克到 3 克不等。尽管受试者数量有限，但该研究允许假设日剂量与深色头发的浓度之间可能存在相关性，而对于浅色头发则没有发现相关性。

更新日期：2020-06-28

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