Determination of Bis(9)-(-)-Meptazinol, a bis-ligand for Alzheimer's disease, in rat plasma by liquid chromatography-tandem mass spectrometry: application to pharmacokinetics study.
A rapid, simple and sensitive LC-MS/MS method was developed and validated for the determination of Bis(9)-(-)-Meptazinol (B9M) in rat plasma. Protein precipitation method was used for sample preparation, using five volumes of methanol as the precipitation agent. The analytes were separated by a Zorbax Extend-C18 column with the mobile phase of methanol-water (containing 5mM ammonium formate, pH 9.8) (95:5, v/v), and monitored by positive electrospray ionization in multiple reaction monitoring (MRM) mode. Retention time of IS (Bis(5)-(-)-Meptazinol) and B9M were 1.9 min and 3.3 min, respectively. The limit of detection was 0.1 ng/ml and the linear range was 1-500 ng/ml. The relative standard deviation (RSD) of intra-day and inter-day variation was 4.4-6.2% and 6.2-8.9%, respectively. The extraction recoveries of B9M in plasma were over 95%. The method proved to be applicable to the pharmacokinetic study of B9M in rat after intravenous and subcutaneous administration.
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, PR China.
Xin-xing
XX
Ge
Xiao-lin
XL
Wang
Pan
P
Jiang
Ying
Y
Xie
Tao
T
Jiang
Zheng-xing
ZX
Rong
Qi-zhi
QZ
Zhang
Qiong
Q
Xie
Zhui-bai
ZB
Qiu
Hao
H
Wang
Hong-zhuan
HZ
Chen
D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy; D000818:Animals; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008621:Meptazinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000432:Methanol; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002800:Cholinesterase Inhibitors; D008621:Meptazinol; D000432:Methanol