Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2G3, Canada.
Anal Bioanal Chem. 2013 Feb;405(6):1903-11. doi: 10.1007/s00216-012-6700-5. Epub 2013 Jan 15.
Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL patients over three consecutive days. The patients received 10 mg arsenic trioxide each day via intravenous infusion. The saliva samples were analyzed using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Monomethylarsonous acid and monomethylmonothioarsonic acid were identified along with arsenite, dimethylarsinic acid, monomethylarsonic acid, and arsenate. Arsenite was the predominant arsenic species, accounting for 71.8 % of total arsenic in the saliva. Following the arsenic infusion each day, the percentage of methylated arsenicals significantly decreased, possibly suggesting that the arsenic methylation process was saturated by the high doses immediately after the arsenic infusion. The temporal profiles of arsenic species in saliva following each arsenic infusion over 3 days have provided information on arsenic exposure, metabolism, and excretion. These results suggest that saliva can be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients.
三氧化二砷已成功用于治疗急性早幼粒细胞白血病(APL)。详细监测 APL 患者各种可及标本中的治疗用砷及其代谢物有助于提高治疗效果并最小化砷诱导的副作用。本文重点介绍了在接受砷治疗的 APL 患者的唾液样本中测定砷形态。采集了 9 名 APL 患者连续 3 天的唾液样本。患者每天通过静脉输注接受 10 毫克三氧化二砷。采用高效液相色谱-电感耦合等离子体质谱联用技术对唾液样本进行分析。鉴定出了一甲基胂酸和一甲基亚砷酸,以及亚砷酸盐、二甲基砷酸、一甲基砷酸和砷酸盐。亚砷酸盐是主要的砷形态,占唾液中总砷的 71.8%。每天输注砷后,甲基化砷的百分比显著下降,这可能表明在高剂量的砷输注后,砷的甲基化过程立即饱和。3 天内每次砷输注后唾液中砷形态的时间谱提供了砷暴露、代谢和排泄的信息。这些结果表明,唾液可用作监测 APL 患者砷形态的合适临床生物标志物。