The antiviral drug acyclovir (ACV) may induce drug-induced neuropsychiatric symptoms as side effects. The detailed pathogenic mechanism remains unclear; however, it is hypothesized that 9-carboxymethoxymethylguanine (CMMG), a metabolite of ACV, is the causative compound. Therefore, the blood concentrations of ACV and CMMG should be analyzed in ACV toxicity studies. However, it is rare to find methods that can sufficiently separate the ACV and CMMG peaks during simultaneous analysis of both compounds. Therefore, we intended to develop a liquid chromatography tandem mass spectrometry method with improved peak separation of analytes. Samples were deproteinized using methanol/acetonitrile solution (6:4, v/v). Analytes were separated on an InertSustain® Amide column (3 μm, 2.1 × 150 mm). The mobile phase consisted of acetonitrile/10 mM ammonium formate (5:95, v/v) (A) and acetonitrile/10 mM ammonium formate (95:5, v/v, pH 5.0) (B) and samples were eluted in the gradient mode. The separation of analytes was satisfactory and the peak shapes were good. Linear regression models weighted 1/x2 were obtained in the range of 0.25–10 μg/mL. The range of quality control (QC) bias was between 3.6 and 19.8%, and the within-run and between-run precisions of QC were within 13.5%. Recovery ranged from 83.6 to 103.7%, but ion suppression was observed. Samples from a patient with ACV encephalopathy were analyzed using this method. The resulting blood ACV and CMMG concentrations were 8.2 and 8.5 μg/mL, respectively. This method, with sufficient separation of ACV and CMMG, proved useful for use in ACV toxicity studies.

中文翻译：

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亲水相互作用液相色谱串联质谱法同时分析阿昔洛韦及其代谢物

抗病毒药物阿昔洛韦（ACV）可能会引起药物引起的神经精神症状作为副作用。详细的致病机制尚不清楚；然而，据推测，ACV 的代谢物 9-羧基甲氧基甲基鸟嘌呤 (CMMG) 是致病化合物。因此，ACV毒性研究中应分析ACV和CMMG的血液浓度。然而，在同时分析两种化合物时，很少能找到能够充分分离 ACV 和 CMMG 峰的方法。因此，我们打算开发一种液相色谱串联质谱方法，以改善分析物的峰分离。使用甲醇/乙腈溶液（6:4，v/v）对样品进行脱蛋白。在 InertSustain® Amide 柱（3 μm，2.1 × 150 mm）上分离分析物。流动相由乙腈/10 mM 甲酸铵 (5:95, v/v) (A) 和乙腈/10 mM 甲酸铵 (95:5, v/v, pH 5.0) (B) 组成，样品在渐变模式。分析物的分离令人满意并且峰形良好。在 0.25–10 μg/mL 范围内获得加权 1/x2 的线性回归模型。质量控制 (QC) 偏差范围在 3.6% 至 19.8% 之间，批内和批间精密度在 13.5% 以内。回收率范围为 83.6% 至 103.7%，但观察到离子抑制。使用这种方法对 ACV 脑病患者的样本进行了分析。所得血液 ACV 和 CMMG 浓度分别为 8.2 和 8.5 μg/mL。该方法充分分离了 ACV 和 CMMG，被证明可用于 ACV 毒性研究。