Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS
Qiaoli Shi,
Mingyan Ju,
Xiaoxia Zhu,
Hui Gan,
Ruolan Gu,
Zhuona Wu,
Zhiyun Meng,
Guifang Dou
Affiliations
Qiaoli Shi
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
Mingyan Ju
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
Xiaoxia Zhu
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
Hui Gan
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
Ruolan Gu
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
Zhuona Wu
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
Zhiyun Meng
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
Guifang Dou
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China
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 (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) 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−1 (measured as As), with r > 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−1; 0.61 mg·kg−1 of arsenic); in addition, the absolute oral bioavailability of the active ingredient AsIII of arsenic trioxide in cynomolgus macaque samples was derived as 60.9 ± 16.1%.
