Speciation analysis of arsenic in urine samples from APL patients treated with single agent As2O3 by HPLC-HG-AFS

Publication date: Available online 8 April 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Meihua Guo, Jing Li, Shengjin Fan, Wensheng Liu, Bin Wang, Chunlu Gao, Jin Zhou, Xin HaiAbstractArsenic trioxide [As2O3, arsenite (AsIII) 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 [AsIII and its metabolites, monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), and arsenate (AsV)] in urine samples from 66 patients with APL. Patients received As2O3 (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: AsIII, 33.00% (IQR: 24.34% to 46.82%); DMAV, 36.42% (IQR: 25.82% to 51.98%); MMAV, 23.89% (IQR: 19.52% to 27.19%); and AsV, 2.22% (IQR: 1.293% to 3.665%). The levels and proportions of arsenic species vary widely among individual patients. DMAV and un-metabolized AsIII were the dominant arsenic compounds excreted from the urine of patients with APL treated with As2O3. AsV was the least abundant arsenic species ...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research