Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Hematology, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Heilongjiang Institute of Hematology & Oncology, Harbin, China.
J Pharm Biomed Anal. 2019 Jul 15;171:212-217. doi: 10.1016/j.jpba.2019.04.014. Epub 2019 Apr 8.
Arsenic trioxide [AsO, arsenite (As) in solution] has been applied successfully for the treatment of acute promyelocytic leukemia (APL). The arsenic speciation analysis of urine is critical to reveal the metabolic mechanism and the relationship between arsenic species and the clinical response. To characterize the arsenic species in urine, a simple and robust HPLC-HG-AFS method was developed and validated to quantify the levels of arsenic species [As and its metabolites, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenate (As)] in urine samples from 66 patients with APL. Patients received AsO (0.16 mg/kg/day) via continuous slow-rate infusion or conventional infusion. Urine samples were collected at steady state before the start of the next daily administration. The relative proportions (median) of arsenic species in urine were: As, 33.00% (IQR: 24.34%-46.82%); DMA, 36.42% (IQR: 25.82%-51.98%); MMA, 23.89% (IQR: 19.52%-27.19%); and As, 2.22% (IQR: 1.293%-3.665%). The levels and proportions of arsenic species vary widely among individual patients. DMA and un-metabolized As were the dominant arsenic compounds excreted from the urine of patients with APL treated with AsO. As was the least abundant arsenic species in all urine samples. Good positive correlations were found between the levels and proportions of arsenic species in urine and those in plasma; thus, urinary arsenic can reflect the levels of arsenic in plasma. Urinary arsenic is a critical biomarker to evaluate the metabolism and toxicity of arsenic in the clinical application of AsO.
三氧化二砷（AsO，溶液中的亚砷酸盐（As））已成功应用于治疗急性早幼粒细胞白血病（APL）。尿液中砷的形态分析对于揭示代谢机制以及砷形态与临床反应之间的关系至关重要。为了对尿液中的砷形态进行特征分析，建立并验证了一种简单而强大的 HPLC-HG-AFS 方法，用于定量测定 66 例 APL 患者尿液样本中砷形态（砷及其代谢物，一甲基砷酸（MMA），二甲基砷酸（DMA）和砷酸盐（As））的水平。患者接受 AsO（0.16mg/kg/天）连续慢滴注或常规滴注。在开始下一次每日给药前，在稳定状态下采集尿液样本。尿液中砷形态的相对比例（中位数）为：As，33.00%（IQR：24.34%-46.82%）；DMA，36.42%（IQR：25.82%-51.98%）；MMA，23.89%（IQR：19.52%-27.19%）；As，2.22%（IQR：1.293%-3.665%）。个体患者之间砷形态的水平和比例差异很大。未代谢的 As 和 DMA 是接受 AsO 治疗的 APL 患者尿液中排泄的主要砷化合物。所有尿液样本中 As 的含量最少。尿液中砷形态的水平和比例与血浆中砷形态的水平和比例之间存在良好的正相关；因此，尿液中的砷可以反映血浆中的砷水平。尿液中的砷是评估砷在 AsO 临床应用中的代谢和毒性的关键生物标志物。
