A validated sensitive HPLC-MS/MS method for quantification of a potential hypnotic drug MT502 and its application to a pharmacokinetic study in rat.
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.
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Fang-Fang
FF
Zhang
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Ying
Y
Cheng
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Ning
N
Wan
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Zi-Wei
ZW
Jing
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Jia
J
Ju
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Yi-Yang
YY
Jia
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Si-Yuan
SY
Zhou
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Bang-Le
BL
Zhang
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006993:Hypnotics and Sedatives / Q000032:analysis* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
D006993:Hypnotics and Sedatives
HPLC-MS/MS; melatonin derivatives; pharmacokinetics; rat