Analysis of daunorubicin and its metabolite daunorubicinol in plasma and urine with application in the evaluation of total, renal and metabolic formation clearances in patients with acute myeloid leukemia
Analysis of daunorubicin and its metabolite daunorubicinol in plasma and urine with application in the evaluation of total, renal and metabolic formation clearances in patients with acute myeloid leukemia
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DOI：
10.1016/j.jpba.2020.113576
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发表时间：
2020-11-30
影响因子：
3.4
通讯作者：
Lanchote, Vera Lucia
中科院分区：
文献类型：
--
作者：
de Oliveira, Milena Locci;Rocha, Adriana;Lanchote, Vera Lucia
本报告介绍了柔红霉素（DAUN）及其代谢产物柔红霉素（DAUNOL）在小体积血浆中的总浓度和游离浓度以及尿液中的改进分析方法。本研究还介绍了DAUN和DAUNOL在诊断为急性髓性白血病的患者（n = 12）中的药代动力学，这些患者接受静脉注射DAUN（60 mg/m2/天，持续3天）治疗。在首次输注开始后144 h内采集系列血液和尿液样本。分析方法未显示显著的基质效应。血浆、超滤液和尿液的线性范围分别为0.1-1000 ng/mL、0.05-40 ng/mL和0.5-3000 ng/mL。精密度和准确度的变异系数和标准误均低于15%。该方法允许在首次输注开始后长达144 h对样品进行定量。DAUN和DAUNOL的未结合级分分别为23.91%（17.33-32.99）和29.23%（25.84-33.07）。尿液中回收的DAUN级分为4.40%（3.87-5.03），DAUNOL级分为7.91%（6.86-9.19）。评价了DAUN的总清除率为292.96 L/h（261.74-327.90），肾脏清除率为13.01 L/h（11.44-14.88），肝脏清除率为280.26 L/h（248.40-317.91），以及DAUNOL形成清除率为23.41 L/h（19.09-28.97）。(C)2020爱思唯尔B. V.保留所有权利。
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/m(2)/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. (C) 2020 Elsevier B.V. All rights reserved.