Acetyl triethyl citrate (ATEC) is a water-soluble plasticizer used in pharmaceutical plasticized polymers. In this study, the pharmacokinetics and metabolism of ATEC were investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rats. Plasma protein precipitation with methanol was used for sample preparation. For chromatographic separation, a C18 column was used. The mobile phases consisted of 0.1% formic acid and 90% acetonitrile, and gradient elution was used. The following precursor-product ion pairs were selected for reaction monitoring analysis: 319.1 m/z → 157 m/z for ATEC and 361.2 m/z → 185.1 m/z for tributyl citrate (internal standard) in positive ion mode. The LC-MS/MS method was fully validated and successfully applied to a pharmacokinetic study of ATEC in rats. The pharmacokinetic study showed that the volume of distribution and mean residence time of ATEC were higher after oral administration than after intravenous administration, pointing to extensive first-pass metabolism and distribution in tissue. In addition, the plasma concentration profile of the postulated metabolites of ATEC was investigated in plasma, urine, and feces. The resulting data indicated that ATEC was extensively metabolized and excreted mainly as metabolites rather than as the parent form. The developed analytical method and the data on the pharmacokinetics and metabolism of ATEC may be useful for understanding the safety and toxicity of ATEC.

中文翻译：

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乙酰柠檬酸三乙酯（一种水溶性增塑剂，用于大鼠体内的高分子药物）的药代动力学和代谢。

乙酰柠檬酸三乙酯（ATEC）是用于药物增塑聚合物的水溶性增塑剂。在这项研究中，使用液相色谱-串联质谱（LC-MS / MS）在大鼠中研究了ATEC的药代动力学和代谢。用甲醇沉淀血浆蛋白用于样品制备。为了色谱分离，使用C18柱。流动相由0.1％的甲酸和90％的乙腈组成，并使用梯度洗脱。选择了以下前体-产物离子对进行反应监测分析：正离子模式下，ATEC为319.1 m / z→157 m / z，柠檬酸三丁酯（内标）为361.2 m / z→185.1 m / z。LC-MS / MS方法已得到充分验证，并成功应用于大鼠ATEC的药代动力学研究。药代动力学研究表明，口服给药后ATEC的分布体积和平均停留时间均高于静脉给药后，表明广泛的首过代谢和在组织中的分布。此外，还对血浆，尿液和粪便中假定的ATEC代谢产物的血浆浓度进行了研究。所得数据表明，ATEC被广泛代谢和排泄，主要是作为代谢产物而不是母体形式。发达的分析方法以及有关ATEC药代动力学和代谢的数据可能有助于理解ATEC的安全性和毒性。此外，还对血浆，尿液和粪便中假定的ATEC代谢产物的血浆浓度进行了研究。所得数据表明，ATEC被广泛代谢和排泄，主要是作为代谢产物而不是母体形式。所开发的分析方法以及ATEC的药代动力学和代谢数据可能有助于理解ATEC的安全性和毒性。此外，还对血浆，尿液和粪便中假定的ATEC代谢产物的血浆浓度进行了研究。所得数据表明，ATEC被广泛代谢和排泄，主要是作为代谢产物而不是母体形式。发达的分析方法以及有关ATEC药代动力学和代谢的数据可能有助于理解ATEC的安全性和毒性。