High-pressure liquid chromatographic methods for determining arabinosyladenine-5'-monophosphate, arabinosyladenine, and arabinosylhypoxanthine in plasma and urine.
New high-pressure liquid chromatographic methods for determining concentrations of arabinosyladenine (Ara-A), its 5'-monophosphate (Ara-AMP), and arabinosylhypoxanthine (Ara-H) in plasma and urine are presented. A fluorescence detector is used for Ara-A and Ara-AMP, which are first converted to highly fluorescent derivatives with chloroacetaldehyde. This increases sensitivity greatly over previous methods. The sensitivities of the methods (in micrograms per milliliter) are as follows: in plasma, Ara-AMP, 0.002; Ara-A, 0.0015; and Ara-H, 0.35; and in urine, 9 times these values, respectively. Drug concentration data are also presented, which were obtained after doses of Ara-AMP were given intramuscularly to two patients treated with this drug for severe herpes zoster. One patient was given 13 mg of Ara-AMP per kg of body weight once daily, and the other was given 6.5 mg/kg twice daily. Peak Ara-AMP and Ara-A levels in plasma occurred within 1 h after the doses, and neither exceeded 2 micrograms/ml. Ara-AMP and Ara-A concentrations in plasma fell to less than 0.01 micrograms/ml in both patients by 4 to 6 h after the doses. Peak Ara-H concentrations in plasma occurred within 1 to 2 h after doses and were 21 micrograms/ml in patient 1 and 2. The highest concentration of Ara-AMP in urine was 0.09 micrograms/ml. The highest Ara-A concentration in urine was 62 micrograms/ml, and the highest Ara-H concentration in urine was 1,080 micrograms/ml. An interfering substance of unknown nature, cochromatographing with Ara-H, was encountered sporadically in urine samples. An algorithm based on differential spectrophotometry to identify and correct for this problem is described. Estimates of the renal clearances of Ara-AMP, Ara-A, and Ara-H are also given.
W P
WP
McCann
L M
LM
Hall
W
W
Siler
N
N
Barton
R J
RJ
Whitley
D001087:Arabinonucleosides / Q000032:analysis* / Q000378:metabolism; D001088:Arabinonucleotides / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000032:analysis; D006562:Herpes Zoster / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008657:Metabolic Clearance Rate; D014740:Vidarabine / Q000032:analysis* / Q000378:metabolism; D001084:Vidarabine Phosphate / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use
D001087:Arabinonucleosides; D001088:Arabinonucleotides; D001084:Vidarabine Phosphate; C008099:hypoxanthine arabinoside; D003404:Creatinine; D014740:Vidarabine