Abstract
A rapid and sensitive UFLC–MS/MS method was developed for the simultaneous determination of liguzinediol and its four primary metabolites (M1, M2, M3, and M4) in rat plasma using antipyrine as internal standards. The analytes were separated on an XR-ODS column (50 mm × 2.0 mm, 2.2 μm) using 0.1 % formic acid–methanol gradient elution at a flow rate of 0.5 mL·min−1. The detection was performed on a triple quadrupole tandem mass spectrometer in a multiple reaction monitoring mode with positive electrospray ionization. Method validation was performed as per the Food and Drug Administration guidelines. The resulting calibration curves offered satisfactory linearity (r > 0.9993) with the set ranges. The limits of quantification for liguzinediol, M1, M2, M3, and M4 were 20, 20, 21, 27, and 10 ng mL−1, respectively. The recovery rates in different matrices ranged from 91.2 to 114.1 %, and the inter-day and intra-day precisions were all less than 13.4 % for the target analytes. After validation, this method was successfully applied to further study pharmacokinetics profiles of liguzinediol and its metabolites after intravenous administration of 10 mg·kg−1 in male and female rats.
Similar content being viewed by others
References
Li W, Chen L (2012) Application of 2,5-dihydroxymethyl-3,6-dimethylpyrazine and its derivatives in pharmacy. US Patent 8,158,630
Lubsen J, Just H, Hjalmarsson AC (1996) Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart 76(3):223–231
Zhao HP, Lü D, Zhang W (2010) Protective action of tetramethylpyrazine phosphate against dilated cardiomyopathy in cTnT(R141 W) transgenic mice. Acta Pharmacol Sin 31(3):281–288
Cohn JN, Goldstein SO, Greenberg BH (1998) A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. New Engl J Med 339(25):1810–1816
Liu Z, Li W, Wen HM (2013) Synthesis, biological evaluation, and pharmacokinetic study of novel liguzinediol prodrugs. Molecules 18(4):4561–4572
Zhang J, Li W, Wen HM (2014) Synthesis and biological evaluation of liguzinediol mono- and dual ester prodrugs as promising inotropic agents. Molecules 19(11):18057–18072
Chen L, Xu Y, Li W, Wu H (2012) The novel compound liguzinediol exerts positive inotropic effects in isolated rat heart via sarcoplasmic reticulum Ca2+ ATPase-dependent mechanism. Life Sci 91:402–403
Li Y, Song P, Zhu Q (2014) Liguzinediol improved the heart function and inhibited myocardial cell apoptosis in rats with heart failure. Acta Pharmacol Sin 35(10):1257–1264
Shan CX, Li W, Wen HM (2011) Determination of Liguzinediol and its pharmacokinetics in rat by ultra performance of liquid chromatograph. Chin Pharmacol Bull 27(5):709–712
Zhang L, Li W, Wen HM (2013) An LC-MS/MS method for determining liguzinediol in rat plasma and studying its pharmacokinetics. Chin J New Drugs 22(9):1024–1028
Shan CX, Li W, Wen HM (2012) Identification of liguzinediol metabolites in rats by ultra-performance liquid Chromatography/quadrupole-time-of-flight mass spectrometry. J Pharm Biom Anal 62:187–188
Shan CX, Li W, Wen HM (2014) Metabolite identification of liguzinediol in dogs by ultra-flow liquid chromatography/tandem mass spectrometry. J Chromatogr B 967:63–68
HH Zhu, YQ Chen, D Cheng (2015) Synthesis and positive inotropic activity evaluation of liguzinediol metabolites. Bioorg Med Chem Lett. In Press, Corrected Proof, Available online
US Food and Drug Administration (2013) Guidance for industry: bioanalytical method validation. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm368107.pdf. Accessed 5 Sept 2013
Acknowledgments
This work was supported by the National Science Foundation of China (No 81573304), Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20123237110010), and Research Fund for Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXM-2-1). This study was also supported by a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (2014-2017).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest.
Rights and permissions
About this article
Cite this article
You, X., Wen, H., Wang, X. et al. Study on Pharmacokinetics of Liguzinediol and Four Metabolites in Rats by UFLC–MS/MS. Chromatographia 79, 703–710 (2016). https://doi.org/10.1007/s10337-016-3072-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10337-016-3072-6