A validated sensitive HPLC‐MS/MS method for quantification of a potential hypnotic drug MT502 and its application to a pharmacokinetic study in rat |
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Authors: | Fang‐Fang Zhang Ying Cheng Ning Wan Zi‐Wei Jing Jia Ju Yi‐Yang Jia Si‐Yuan Zhou Bang‐Le Zhang |
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Affiliation: | Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, People's Republic of China |
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Abstract: | 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. Copyright © 2015 John Wiley & Sons, Ltd. |
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Keywords: | melatonin derivatives HPLC-MS/MS pharmacokinetics rat |
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