Development and validation of a rapid LC-MS/MS method for simultaneous determination of netupitant and palonosetron in human plasma and its application to a pharmacokinetic study.
A simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was firstly developed and validated for simultaneous determination of netupitant and palonosetron in human plasma using ibrutinib as the internal standard (IS). Following liquid-liquid extraction, the compounds were eluted isocratically on a Phenomenex C18 column (50mm×2.0mm, 3μm) with the mobile phase consisting of acetonitrile and 10mM ammonium acetate buffer (pH 9.0) (89:11, v/v) at the flow rate of 0.3mL/min. The monitored ion transitions were m/z 579.5→522.4 for netupitant, m/z 297.3→110.2 for palonosetron and m/z 441.2→138.1 for IS. Chromatographic run time was 2.5min per injection, which made it possible to analyze more than 300 of samples per day. The assay exhibited a linear dynamic range of 5-1000ng/mL for netupitant and 0.02-10ng/mL for palonosetron in plasma. The values for both within- and between-day precision and accuracy were well within the generally accepted criteria for analytical methods (<15%). Selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, stability, matrix effect, recovery and carry-over effect were evaluated for all analytes. The method is simple, rapid, and has been applied successfully to a pharmacokinetic study of netupitant and palonosetron in healthy volunteers.
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Mingzhen
M
Xu
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Yang
Y
Ni
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Shihong
S
Li
College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, PR China.
Juan
J
Du
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Huqun
H
Li
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Ying
Y
Zhou
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic address: wenzhangsci@163.com.
Weiyong
W
Li
Department of Infectious Disease, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic address: shining119@163.com.
Hui
H
Chen
D000932:Antiemetics / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods*; D006801:Humans; D007546:Isoquinolines / Q000097:blood*; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000191:economics / Q000379:methods; D000077924:Palonosetron; D011725:Pyridines / Q000097:blood*; D011812:Quinuclidines / Q000097:blood*; D012702:Serotonin Antagonists / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D013997:Time Factors; D010879:Piperazines; D044482:Benzeneacetamides
D000932:Antiemetics; D007546:Isoquinolines; D000077924:Palonosetron; D011725:Pyridines; D011812:Quinuclidines; D012702:Serotonin Antagonists; C508854:netupitant; D010879:Piperazines; D044482:Benzeneacetamides
Human plasma; LC–MS/MS; Netupitant; Palonosetron; Pharmacokinetics