title: Development, evaluation and application of an isocratic high-performance liquid chromatography (HPLC) assay for the simultaneous determination of aciclovir and its metabolite 9-carboxymethoxymethylguanine in human serum and cerebrospinal fluid.
abstract: 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.
authors.affiliation: Bristol Centre for Antimicrobial Research & Evaluation, Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK. mervyn.darville@nbt.nhs.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Darville
authors.forename: A M
authors.initials: AM
authors.lastname: Lovering
authors.forename: A P
authors.initials: AP
authors.lastname: MacGowan
mesh_terms: D000212:Acyclovir / Q000032:analysis*; D000704:Analysis of Variance; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044967:Serum / Q000737:chemistry*
chemical_list: D006147:Guanine; C035400:9-carboxymethoxymethylguanine; D000212:Acyclovir