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Rapid high-performance liquid chromatographic assay for the anthracyclines daunorubicin and 7-con-O-methylnogarol in plasma

1981; Elsevier BV; Volume: 226; Issue: 2 Linguagem: Inglês

10.1016/s0378-4347(00)86092-2

1872-812X

John E. Brown, Paul A. Wilkinson, Jeffrey Brown,

Cancer Treatment and Pharmacology

This report presents improved analysis methods of daunorubicin (DAUN) and its metabolite daunorubicinol (DAUNOL) in small volumes of plasma, as total and unbound concentrations, as well as in urine. This study also presents the pharmacokinetics of DAUN and DAUNOL in patients (n = 12) diagnosed with acute myeloid leukemia treated with intravenous DAUN (60 mg/m2/day, for three days). Serial blood and urine samples were collected up to 144 h after the beginning of the first infusion. The analytical methods presented no significant matrix effect. The linear ranges were 0.1–1000 ng/mL in plasma, 0.05–40 ng/mL in ultrafiltrate and 0.5–3000 ng/ml in urine. The precision and accuracy presented coefficients of variation and standard errors lower than 15 % in the three matrices. The methods allowed for the quantification of samples up to 144 h after the beginning of the first infusion. Unbound fractions for DAUN and DAUNOL were 23.91 % (17.33–32.99) and 29.23 % (25.84–33.07), respectively. The fraction recovered in urine was 4.40 % (3.87–5.03) for DAUN and 7.91 % (6.86–9.19) for DAUNOL. Total 292.96 L/h (261.74–327.90), renal 13.01 L/h (11.44–14.88), and hepatic 280.26 L/h (248.40–317.91) clearances of DAUN, as well as the DAUNOL formation clearance 23.41 L/h (19.09–28.97), were evaluated.