Metformin is widely used as one of the most effective first-line oral drugs for type 2 diabetes. It is difficult to be metabolized by the human body thus commonly exists in both urine and feces samples. Guanylurea is metformin’s main biotransformation product with increased concentrations in the aquatic environments. Liquid chromatography-tandem mass spectrometry (LC-MS)-based methods used for measuring the two compounds have been well developed, but extremely limited studies have tracked gas chromatography-mass spectrometry (GC-MS)-based analysis. To help better track the occurrence of the two non-volatile biguanide compounds in liquid samples, the improvement of existing GC-MS based methods for reliable metformin and guanylurea analysis is conducted. Derivatization of metformin and guanylurea is the key pretreatment procedure before the associated GC-MS analysis. Four selected factors affecting for the derivatization were evaluated, and the optimal factors include temperature (90°C), reacting time (40 min), solvent (1,4-dioxane), and ratio (1.5:1) of reagent to target component. Buformin and N-methyl-bis(trifluoroacetamide) (MBTFA) were used as the internal standard and the derivatization reagent, respectively. Calibration curves were made based on the optimal conditions of derivatization for metformin and guanylurea with the R² values of calibration linearity achieved as 99.35% and 99.2%, respectively. The values of relative standard deviation (RSD%) of metformin and guanylurea based on seven repeated trails are 2.67% and 15.37%, respectively. The optimal conditions for enhancing the sensitization of metformin and guanylurea derivatization performance were obtained. The improved GC-MS analysis method was eventually applied for metformin and guanylurea analysis in real water samples.

二甲双胍被广泛用作2型糖尿病最有效的一线口服药物之一。尿液和粪便样品中普遍存在人体难以代谢的情况。鸟嘌呤脲是二甲双胍的主要生物转化产物，在水生环境中的浓度增加。用于测量这两种化合物的基于液相色谱-串联质谱（LC-MS）的方法已经得到了很好的开发，但是对基于气相色谱-质谱（GC-MS）的分析的研究非常有限。为了帮助更好地跟踪液体样品中两种非挥发性双胍化合物的发生，对现有基于GC-MS的可靠二甲双胍和鸟嘌呤分析方法进行了改进。二甲双胍和鸟嘌呤的衍生化是相关GC-MS分析之前的关键预处理程序。评估了影响衍生化的四个因素，最佳因素包括温度（90°C），反应时间（40分钟），溶剂（1,4-二恶烷）和试剂与目标组分的比例（1.5：1） 。Buformin和N-甲基-双（三氟乙酰胺）（MBTFA）分别用作内标和衍生试剂。根据二甲双胍和鸟脲的最佳衍生条件绘制校正曲线。Buformin和N-甲基-双（三氟乙酰胺）（MBTFA）分别用作内标和衍生试剂。根据二甲双胍和鸟脲的最佳衍生条件绘制校正曲线。Buformin和N-甲基-双（三氟乙酰胺）（MBTFA）分别用作内标和衍生试剂。根据二甲双胍和鸟脲的最佳衍生条件绘制校正曲线。校准线性度的R ²值分别达到99.35％和99.2％。基于7条重复试验的二甲双胍和鸟尿素的相对标准偏差（RSD％）值分别为2.67％和15.37％。获得了增强二甲双胍敏化和鸟嘌呤脲衍生性能的最佳条件。改进的GC-MS分析方法最终用于实际水样中的二甲双胍和鸟尿素分析。