LC-ESI-MS/MS determination of simotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor: application to a pharmacokinetic study.
Simotinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor. This study presented a sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method using erlotinib as internal standard for the determination of simotinib in human plasma. The method involved a simple liquid-liquid extraction using diethyl ether. The analytes were separated with isocratic gradient elution on an Agilent TC-C18 column (4.6 × 150 mm, 5 μm). Mass spectrometric detector equipped with electrospray ionization source was carried out in the mode of multiple reaction monitoring (MRM). The monitored transitions were m/z 501.2→182.1 for simotinib and m/z 394.4→278.1 for erlotinib. The calibration curve of simotinib was established over the range of 2.058-3000 μg L(-1) (r(2)=0.9924). The intra- and inter-day precisions were all less than 10%, and all the biases were not more than 7%. This validated method was then successfully applied to a pharmacokinetic study involving twelve healthy Chinese volunteers. The mean Cmax and Tmax for simotinib were 254.79±98.30 μg L(-1) and 1.71±0.48 h, respectively. Plasma concentrations declined with a t1/2 of 5.37±2.32 h. AUC0-t and AUC0→∞ values obtained were 1262.59±501.41 μg L(-1) h and 1329.95±517.42 μg L(-1) h, respectively.
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Lihua
L
He
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Sanwang
S
Li
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Feifan
F
Xie
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Zeneng
Z
Cheng
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Liling
L
Ran
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China.
Xingling
X
Liu
School of Pharmaceutical Sciences, Central South University, Changsha 410013, PR China. Electronic address: peng.yu@csu.edu.cn.
Peng
P
Yu
D000293:Adolescent; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000097:blood / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013141:Spiro Compounds / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013141:Spiro Compounds; C000591834:N-(3-chloro-4-fluorophenyl)-6-(2-(5, 8-dioxa-11-azadispiro(2.0.4.3)undec-11-yl)ethoxy)-7-methoxy-4-quinazolinamine; D066246:ErbB Receptors
High performance liquid chromatography-electrospray ionization-mass spectrometry; Human plasma; Pharmacokinetics; Simotinib