Ln. Long et al., Determination of 8-oxoguanine in human plasma and urine by high-performance liquid chromatography with electrochemical detection, J CHROMAT B, 731(2), 1999, pp. 241-249
A highly sensitive and selective method for determining 8-oxoguanine in pla
sma and urine was developed by high-performance liquid chromatography with
electrochemical detection. The compound was separated by gradient elution o
n a C-18 reversed-phase column with a mobile phase of acetonitrile and 0.1
M sodium acetate, pH 5.2. 8-Hydroxy-2'-deoxyguanosine was used as internal
standard. 8-Oxoguanine was detected electrochemically by setting the potent
ial to +300 mV vs. Pd reference. The sensitivity of the assay was 22 ng/ml
with a signal-to-noise ratio of 7:1. The within-day relative standard devia
tions for 8-oxoguanine quality control samples with concentrations of 3340,
1340 and 84 ng/ml were 3.6, 4.3 and 5.7% for plasma, and 4.1, 4.6 and 6.2%
for urine, respectively. The day-to-day relative standard deviations for t
he same samples were 3.8, 6.8 and 7.1% for plasma, and 3.9, 7.0 and 7.9% fo
r urine, respectively. The method is designed to study the pharmacokinetics
and metabolic fate of O-6-benzylguanine in a phase I clinical trial. Previ
ously, O-6-benzyl-8-oxoguanine was identified as the primary metabolite of
O-6-benzylguanine in humans. We now demonstrate that 8-oxoguanine is a furt
her metabolite of O-6-benzylguanine. (C)1999 Elsevier Science B.V. All righ
ts reserved.