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An LC-MS/MS method for simultaneous determination of trantinterol and its major metabolite in rat plasma and its application to a comparative pharmacokinetic study.

Abstract

Trantinterol is a novel β2-adrenoceptor agonist, currently undergoing clinical trials for the treatment of asthma. We developed and validated an liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of trantinterol and its major metabolite, 1-carbonyl trantinterol (SPFFCOOH), in rat plasma. Aliquots (100μL) of heparinized plasma samples were processed by protein precipitation with acetonitrile. Chromatographic separation used an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) and acetonitrile-0.1% formic acid (20:80, v/v) as mobile phase, at a flow rate of 0.25mL/min. The detection was performed on a triple-quadrupole tandem mass spectrometer with multiple-reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The precursor-to-product ion transitions m/z 310.9→m/z 237.9 for trantinterol, m/z 324.9→m/z 251.9 for SPFFCOOH and m/z 368.0→m/z 294.0 for bambuterol (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentration of 0.25-100ng/mL for both trantinterol and SPFFCOOH. The intra- and inter-day precision (relative standard deviations, RSD) values were below 15% and accuracy (relative error, RE) was from -4.3% to 6.6% at all quality control (QC) levels. The method was successfully applied to compare the pharmacokinetics of trantinterol and SPFFCOOH in male and female Wistar rats after a single oral administration of trantinterol.

Authors+Show Affiliations

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.Jiangsu Kanion Pharmaceutical Co., Ltd, 58 Haichang South Road, Xinpu District, Lianyungang 222001, PR China.School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: machao_syphu@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26245359

Citation

Wang, Yanjuan, et al. "An LC-MS/MS Method for Simultaneous Determination of Trantinterol and Its Major Metabolite in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 1000, 2015, pp. 163-8.
Wang Y, Qin F, Xiong Z, et al. An LC-MS/MS method for simultaneous determination of trantinterol and its major metabolite in rat plasma and its application to a comparative pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2015;1000:163-8.
Wang, Y., Qin, F., Xiong, Z., Fu, X., & Ma, C. (2015). An LC-MS/MS method for simultaneous determination of trantinterol and its major metabolite in rat plasma and its application to a comparative pharmacokinetic study. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1000, 163-8. https://doi.org/10.1016/j.jchromb.2015.07.022
Wang Y, et al. An LC-MS/MS Method for Simultaneous Determination of Trantinterol and Its Major Metabolite in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Sep 1;1000:163-8. PubMed PMID: 26245359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An LC-MS/MS method for simultaneous determination of trantinterol and its major metabolite in rat plasma and its application to a comparative pharmacokinetic study. AU - Wang,Yanjuan, AU - Qin,Feng, AU - Xiong,Zhili, AU - Fu,Xiaohuan, AU - Ma,Chao, Y1 - 2015/07/17/ PY - 2015/01/28/received PY - 2015/07/06/revised PY - 2015/07/08/accepted PY - 2015/8/7/entrez PY - 2015/8/8/pubmed PY - 2016/2/4/medline KW - Comparative pharmacokinetics KW - Determination KW - LC–MS/MS KW - Trantinterol 1-carbonyl trantinterol SP - 163 EP - 8 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. VL - 1000 N2 - Trantinterol is a novel β2-adrenoceptor agonist, currently undergoing clinical trials for the treatment of asthma. We developed and validated an liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of trantinterol and its major metabolite, 1-carbonyl trantinterol (SPFFCOOH), in rat plasma. Aliquots (100μL) of heparinized plasma samples were processed by protein precipitation with acetonitrile. Chromatographic separation used an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) and acetonitrile-0.1% formic acid (20:80, v/v) as mobile phase, at a flow rate of 0.25mL/min. The detection was performed on a triple-quadrupole tandem mass spectrometer with multiple-reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The precursor-to-product ion transitions m/z 310.9→m/z 237.9 for trantinterol, m/z 324.9→m/z 251.9 for SPFFCOOH and m/z 368.0→m/z 294.0 for bambuterol (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentration of 0.25-100ng/mL for both trantinterol and SPFFCOOH. The intra- and inter-day precision (relative standard deviations, RSD) values were below 15% and accuracy (relative error, RE) was from -4.3% to 6.6% at all quality control (QC) levels. The method was successfully applied to compare the pharmacokinetics of trantinterol and SPFFCOOH in male and female Wistar rats after a single oral administration of trantinterol. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/26245359/An_LC_MS/MS_method_for_simultaneous_determination_of_trantinterol_and_its_major_metabolite_in_rat_plasma_and_its_application_to_a_comparative_pharmacokinetic_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(15)30089-1 DB - PRIME DP - Unbound Medicine ER -