Darville J M, Lovering A M, MacGowan A P
Bristol Centre for Antimicrobial Research & Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.
Int J Antimicrob Agents. 2007 Jul;30(1):30-3. doi: 10.1016/j.ijantimicag.2007.02.005. Epub 2007 Apr 10.
9-Carboxymethoxymethylguanine (CMMG), the main metabolite of aciclovir (ACV), is a putative neurotoxin. Measurement of CMMG in body fluids may aid patient management. We describe the development, validation and application of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of ACV and CMMG in human serum and cerebrospinal fluid (CSF). Recovery was between 94% and 100% at all concentrations both from serum (range 0-20 mg/L) and CSF (0-5 mg/L). The intra-assay precision (coefficient of variation (CV)) was <2% and the inter-assay precision (CV) was <5%. The limits of detection and quantification were 0.1 and 0.25 mg/L, respectively, in both body fluids. Significant interference from endogenous material or from drugs in clinical samples was not seen. CMMG was detected in most of the 55 clinical samples containing ACV, but little correlation was found between the levels of the drug and its metabolite.
9-羧甲氧基甲基鸟嘌呤(CMMG)是阿昔洛韦(ACV)的主要代谢产物,是一种潜在的神经毒素。检测体液中的CMMG可能有助于患者管理。我们描述了一种高效液相色谱(HPLC)方法的开发、验证及应用,该方法可同时测定人血清和脑脊液(CSF)中的ACV和CMMG。血清(范围0 - 20 mg/L)和脑脊液(0 - 5 mg/L)在所有浓度下的回收率均在94%至100%之间。批内精密度(变异系数(CV))<2%,批间精密度(CV)<5%。两种体液中的检测限和定量限分别为0.1和0.25 mg/L。未观察到临床样本中内源性物质或药物的显著干扰。在55份含有ACV的临床样本中,大多数检测到了CMMG,但药物及其代谢产物的水平之间几乎没有相关性。