高效液相色谱-电感耦合等离子体质谱法研究三氧化二砷溶液在食蟹猴静脉注射和灌胃给药后的药代动力学特征。
Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS.
机构信息
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China.
Shanghai Yao Jian Medical Biotechnology Limited Company. National University of science and technology, University of Shanghai for Science and Technology, 128 Xiangyin Road, Yangpu District, Shanghai 200433, China.
出版信息
Molecules. 2019 Jan 10;24(2):241. doi: 10.3390/molecules24020241.
A rapid and sensitive method was established for arsenic (As) speciation based on high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). This method was validated for the quantification of four arsenic species, including arsenite (As), arsenate (As), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in cynomolgus macaque plasma. Separation was achieved in just 3.7 min with an alkyl reverse phase column and highly aqueous mobile phase containing 20 mM citric acid and 5 mM sodium hexanesulfonate (pH = 4.3). The calibration curves were linear over the range of 5⁻500 ng·mL (measured as As), with > 0.99. The above method was validated for selectivity, precision, accuracy, matrix effect, recovery, carryover effect and stability, and applied in a comparative pharmacokinetic study of arsenic species in cynomolgus macaque samples following intravenous and intragastrical administration of arsenic trioxide solution (0.80 mg·kg; 0.61 mg·kg of arsenic); in addition, the absolute oral bioavailability of the active ingredient As of arsenic trioxide in cynomolgus macaque samples was derived as 60.9 ± 16.1%.
建立了一种基于高效液相色谱-电感耦合等离子体质谱联用（HPLC-ICP-MS）的砷形态分析快速、灵敏的方法。该方法用于定量检测食蟹猴血浆中的 4 种砷形态，包括亚砷酸盐（As）、砷酸盐（As）、一甲基砷酸（MMA）和二甲基砷酸（DMA）。采用烷基反相柱和高水相流动相（含 20 mM 柠檬酸和 5 mM 己烷磺酸钠，pH = 4.3），仅需 3.7 min 即可实现分离。校准曲线在 5⁻500 ng·mL 范围内（以 As 计）呈线性，相关系数 > 0.99。对该方法进行了选择性、精密度、准确度、基质效应、回收率、交叉污染效应和稳定性验证，并应用于静脉和灌胃给予三氧化二砷溶液（0.80 mg·kg；砷含量分别为 0.61 mg·kg）后食蟹猴样品中砷形态的比较药代动力学研究；此外，还推导了食蟹猴样品中三氧化二砷的活性成分 As 的绝对口服生物利用度为 60.9 ± 16.1%。
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