title: An UPLC-MS/MS method for the quantitation of alectinib in rat plasma.
abstract: Currently, crizotinib is the first generation drug, which has been used in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). However, more and more patients are found in crizotinib-resistance. In the last year, alectinib has been approved for treatment of patients with crizotinib-resistance. In this study, we aim to develop and validate a simple, rapid and sensitive tandem mass spectrometry (UHPLC-MS/MS) method for determination of alectinib in rat plasma. Diazepam was chosen as an internal standard (IS). Protein precipitation by acetonitrile was utilized to prepare plasma samples. Chromatographic separation was achieved on a RRHD Eclipse Plus C18 (2.1×50mm, 1.8μ) column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). The analytes were detected by an electrospray ionization (ESI) source in positive mode. A dynamic multiple reaction monitoring (MRM) method was developed to detect specific precursor and product ions. The target fragment ions were m/z 483.2→396.1 for alectinib and m/z 285.0→192.9 for diazepam (IS). Linear calibration plots were achieved in the range of 1-500ng/ml for alectinib (R2=0.997) in rat plasma. Mean recoveries of alectinib in rat plasma ranged from 84.2% to 92.2%. The intra- and inter-day precision was below 9.3% and accuracy was from -1.4% to 12.1%. No obvious matrix effect was found. This method shows a good performance: accuracy, precision and stability. It has been fully validated and successfully applied to pharmacokinetic study of alectinib.
authors: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Xiang-Xin
authors: XX
authors: Huang
authors: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Yun-Xuan
authors: YX
authors: Li
authors: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Xiang-Yu
authors: XY
authors: Li
authors: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Xiao-Xia
authors: XX
authors: Hu
authors: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Peng-Fei
authors: PF
authors: Tang
authors: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: hgx@wmu.edu.cn.
authors: Guo-Xin
authors: GX
authors: Hu
mesh_terms: D000818:Animals; D002138:Calibration; D002227:Carbazoles / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D010880:Piperidines / Q000097:blood*; D047428:Protein Kinase Inhibitors / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C582670:alectinib
keywords: Alectinib; Pharmacokinetics; Rat plasma; UHPLC–MS/MS