A validated sensitive HPLC-MS/MS method for quantification of a potential hypnotic drug MT502 and its application to a pharmacokinetic study in rat

Autor: Fang-Fang, Zhang, Ying, Cheng, Ning, Wan, Zi-Wei, Jing, Jia, Ju, Yi-Yang, Jia, Si-Yuan, Zhou, Bang-Le, Zhang
Rok vydání: 2014
Předmět:
Zdroj: Biomedical chromatography : BMC. 29(9)
ISSN: 1099-0801
Popis: A rapid, sensitive HPLC-MS/MS method was established and validated to assay the concentration and pharmacokinetic profile of MT502, a promising hypnotic drug. The plasma sample was treated by a liquid-liquid extraction and separated on a kromasil C18 column at an isocratic flow rate of 0.3 mL/min using methanol and 0.1% formic acid in water (75:25, v/v) as mobile phase. The mass spectrometric detection was carried out using a triple-quadrupole system via positive electrospray ionization. Multiple reaction monitoring was used for quantitation of m/z transitions from 261 to 188 for MT502 and from 247 to 188 for MT501 (internal standard). Good linearity was achieved over the concentration range of 1-1000 ng/mL and 10-5000 ng/mL with lower limit of quantification of 0.30 and 0.80 ng/mL. The intra- and inter-day precisions, accuracy, recovery and stability were satisfactory for the concentration test. The above method can be used for a pharmacokinetic study at doses of 1, 5 and 20 mg/kg. Results indicated that MT502 had rapid absorption, rapid elimination and linear pharmacokinetic properties within the range of the tested intragastric dose. This developed HPLC-MS/MS method was successfully applied to a pharmacokinetic study of MT502 for the first time and was demonstrated to be simple and sensitive.
Databáze: OpenAIRE