Qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by liquid chromatography tandem mass spectrometry and its application after intravenous administration of felbinac trometamol injection

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2015-04, Vol.986-987, p.60-68
• Main Authors: Zheng, Yunliang, Hu, Xingjiang, Liu, Jian, Wu, Guolan, Zhai, You, Wu, Lihua, Shentu, Jianzhong
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Chromatography, High Pressure Liquid - methods; Drug Stability; Excretion; Felbinac; HPLC–MS/MS; Human; Humans; Linear Models; Male; Metabolites; Pharmacokinetics; Phenylacetates - administration & dosage; Phenylacetates - blood; Phenylacetates - pharmacokinetics; Phenylacetates - urine; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry - methods; Young Adult
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2015.01.042

•An LC–TOF-MS/MS method was firstly established for identifying metabolites of felbinac in human urine.•An LC–MS/MS method was established and validated for quantitative analysis of felbinac and 4′-hydroxyfelbinac in human plasma and urine.•The comprehensive metabolic pathway, pharmacokinetics and excretion properties of felbinac trometamol in human were proposed for the first time. We present a method for the qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by HPLC–MS/MS and its application. Qualitative analysis through LC–Triple-TOF-MS/MS indicated that oxidization was the main phase-I metabolic pathway of felbinac in human, conjugation with sulfate and glucuronide groups produced at least 7 phase-II metabolites. Quantitative analysis through HPLC–MS/MS in MRM mode was developed and validated for the quantification of felbinac and its major metabolite (4′-hydroxyfelbinac) in human plasma and urine. Linear calibration curves were obtained for felbinac and 4′-hydroxyfelbinac in plasma and urine (r>0.996); intra- and inter-day precision values (RSD%) obtained were ranged from 1.13 to 6.49%, and the accuracy were between 95.9% and 108.6% for the two analytes. The pharmacokinetics and excretion analysis showed that the t1/2 of 4′-hydroxyfelbinac (8.25±4.15h) is a litter longer than that of felbinac (6.13±2.01h), but the mean AUC(0–t) value of felbinac was about 20 times higher than that of 4′-hydroxyfelbinac; excretion of felbinac and 4′-hydroxyfelbinac reached their peak values at about 3–6h after intravenous administration of felbinac trometamol in human.