Application of liquid chromatographic/tandem mass spectrometric method to a urinary excretion study of subutinib and active metabolite in human urine.
A novel and selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and active metabolite in human urine. Urine samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Wondasil C18 (150 × 2.1 mm, 3.5 µm), with methanol-0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2 mL/min. The linear range was 0.5000-200.0 ng/mL for subutinib and active metabolite, with a lower limit of quantitation of 0.5000 ng/mL. Intra- and inter-run precisions were all <11.8 and 14.3%, and the accuracies were all <4.5 and 5.4%, with the extraction recoveries 88.8-97.5 and 93.8-99.4% for the two analytes, respectively. The carryover values were all <15% for the two anayltes. The method was successfully applied to study urinary excretion of subutinib and active metabolite in human after oral administration of subutinib maleate capsules in fed and fasting states.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Li-kun
LK
Ding
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Lin
L
Yang
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Xiao-hua
XH
Gao
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Su-ning
SN
Chen
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Na
N
Jia
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Xue-qing
XQ
Li
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Lun
L
Zhou
Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
Tai-jun
TJ
Hang
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Chang Le West Street 127, Xi'an, Shaanxi, 710032, China.
Ai-dong
AD
Wen
D000328:Adult; D000970:Antineoplastic Agents / Q000378:metabolism / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000652:urine*; D057230:Limit of Detection; D008297:Male; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000652:urine*; D011758:Pyrroles / Q000378:metabolism / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C000607733:subutinib
LC-MS/MS; active metabolite; subutinib; urinary excretion