High-pressure liquid chromatographic methods for determining arabinosyladenine-5'-monophosphate, arabinosyladenine, and arabinosylhypoxanthine in plasma and urine

Academic Article

Abstract

  • 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 μg/ml. Ara-AMP and Ara-A concentrations in plasma fell to less than 0.01 μg/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 μg/ml in patient 1 and 9.7 in patient 2. The highest concentration of Ara-AMP in urine was 0.09 μg/ml. The highest Ara-A concentration in urine was 62 μg/ml, and the highest Ara-H concentration in urine was 1.080 μg/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.
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    Digital Object Identifier (doi)

    Author List

  • McCann WP; Hall LM; Siler W; Barton N; Whitley RJ
  • Start Page

  • 265
  • End Page

  • 273
  • Volume

  • 28
  • Issue

  • 2