UPLC-MS/MS Method for Determination of Khasianine in Mouse Blood: Application for Its Pharmacokinetic Study

Author(s): Lianguo Chen, Qinghua Weng, Yijing Lin, Xiaojie Lu, Zuoquan Zhong, Jianhua Xiong, Xianqin Wang*

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 6 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The aim of this study was to determine the concentrations of khasianine in mouse whole blood sample and its application for the pharmacokinetics by a rapid, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method.

Methods: The blood samples were preprocessed by one-step protein precipitation with acetonitrile. The study was performed on an ACQUITY I-Class UPLC system with a UPLC BEH column. Lannaconitine (internal standard, IS) and khasianine were gradient eluted by a mixture of acetonitrile and water with 0.1% formic acid at a flow rate of 0.4 mL/min. The mass spectrometer was equipped with an Electrospray Ionization (ESI) source in positive mode. The quantitative detection was performed in a multiple reaction monitoring modes at transitions m/z 722.4→70.7 for khasianine and m/z 585.3→119.9 for the corresponding IS.

Results: The calibration curve was of good linearity ranging from 0.5 to 1000 ng/mL (r > 0.995). The Lower Limit of Detection (LLOD) and Lower Limit of Quantitation (LLOQ) were 0.2 and 0.5 ng/mL, respectively. The inter-day and intra-day precision (RSD%) were both less than 14%, and the accuracy ranged from 86.6% to 108.3%. The matrix effects were between 98.0% and 103.7%, and the average recovery was better than 67.4%.

Conclusion: This assay established a sensitive, rapid, selective UPLC-MS/MS method which was successfully used for the pharmacokinetic study of khasianine in mouse blood, and the absolute availability of khasianine was 0.78% which exhibited a poor oral absorption.

Keywords: Khasianine, mouse, UPLC-MS/MS, determination, pharmacokinetics, bioavailability, chinese herbal medicine, pharmacology.

[1]
Akter, R.; Uddin, S.J.; Tiralongo, J.; Grice, I.D.; Tiralongo, E. A new cytotoxic steroidal glycoalkaloid from the methanol extract of blumea lacera leaves. J. Pharm. Pharm. Sci., 2015, 18(4), 616-633.
[http://dx.doi.org/10.18433/J3161Q] [PMID: 26626252]
[2]
Jiang, Q.W.; Chen, M.W.; Cheng, K.J.; Yu, P.Z.; Wei, X.; Shi, Z. Therapeutic potential of steroidal alkaloids in cancer and other diseases. Med. Res. Rev., 2016, 36(1), 119-143.
[http://dx.doi.org/10.1002/med.21346] [PMID: 25820039]
[3]
Gan, K.H.; Lin, C.N.; Won, S.J. Cytotoxic principles and their derivatives of Formosan Solanum plants. J. Nat. Prod., 1993, 56(1), 15-21.
[http://dx.doi.org/10.1021/np50091a003] [PMID: 8450317]
[4]
Yuan, H.; Chen, Y.; Cai, B.; Jia, X.; Chen, Y. [Simultaneous determination of three steroidal alkaloids from Solanum Nigrum by RP-HPLC]. Zhongguo Zhongyao Zazhi, 2011, 36(12), 1630-1632.
[PMID: 22007549]
[5]
Shanker, K.; Gupta, S.; Srivastava, P.; Srivastava, S.K.; Singh, S.C.; Gupta, M.M. Simultaneous determination of three steroidal glycoalkaloids in Solanum xanthocarpum by high performance thin layer chromatography. J. Pharm. Biomed. Anal., 2011, 54(3), 497-502.
[http://dx.doi.org/10.1016/j.jpba.2010.09.025] [PMID: 20965683]
[6]
Chen, L.G.; Wang, Z.; Wang, S.; Li, T.; Pan, Y.; Lai, X. Determination of Apremilast in rat plasma by UPLC-MS-MS and its application to a pharmacokinetic study. J. Chromatogr. Sci., 2016, 54(8), 1336-1340.
[http://dx.doi.org/10.1093/chromsci/bmw072] [PMID: 27165568]
[7]
Chen, L.G.; Su, K.; Lin, Z.X.; Zhang, J.; Xu, H.B.; Zhang, Q.L.; Wang, S.H.; Wen, C.C.; Zhou, Y.F. Pharmacokinetic study of tussilagone in rat plasma by UPLC-MS/MS. Lat. Am. J. Pharm., 2016, 35, 2108-2112.
[8]
US Department of Health and Human Services FaDA. Guidance for Industry: Bioanalytical Method Validation, 2013.
[9]
Xu, W.; Zhang, Y.; Zhou, C.; Tai, Y.; Zhang, X.; Liu, J.; Sha, M.; Huang, M.; Zhu, Y.; Peng, J.; Lu, J.J. Simultaneous quantification six active compounds in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study of Pien-Tze-Huang. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1061-1062, 314-321.
[http://dx.doi.org/10.1016/j.jchromb.2017.07.033] [PMID: 28778039]
[10]
Wang, Z.; Zhao, Q.; Li, L.; Hu, P.; Dong, K.; Chen, S.; Jiang, J. Development and validation of a rapid and sensitive UPLC-MS/MS method for quantification of kukoamine B in human plasma: Application to a clinical pharmacokinetic study. J. Pharm. Biomed. Anal., 2017, 132, 1-6.
[http://dx.doi.org/10.1016/j.jpba.2016.09.032] [PMID: 27693755]
[11]
Li, Y.; Lin, G.; Chen, B.; Zhang, J.; Wang, L.; Li, Z.; Cao, Y.; Wen, C.; Yang, X.; Cao, G.; Wang, X.; Cao, G. Effect of alprazolam on rat serum metabolic profiles. Biomed. Chromatogr., 2017, 31(9), 31.
[http://dx.doi.org/10.1002/bmc.3956] [PMID: 28187228]
[12]
Caban, M.; Migowska, N.; Stepnowski, P.; Kwiatkowski, M.; Kumirska, J. Matrix effects and recovery calculations in analyses of pharmaceuticals based on the determination of β-blockers and β-agonists in environmental samples. J. Chromatogr. A, 2012, 1258, 117-127.
[http://dx.doi.org/10.1016/j.chroma.2012.08.029] [PMID: 22935728]
[13]
Szeitz, A.; Manji, J.; Riggs, K.W.; Thamboo, A.; Javer, A.R. Validated assay for the simultaneous determination of cortisol and budesonide in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry. J. Pharm. Biomed. Anal., 2014, 90, 198-206.
[http://dx.doi.org/10.1016/j.jpba.2013.12.006] [PMID: 24389462]
[14]
Zhang, Q.; Wen, C.; Xiang, Z.; Ma, J.; Wang, X. Determination of CUDC-101 in rat plasma by liquid chromatography mass spectrometry and its application to a pharmacokinetic study. J. Pharm. Biomed. Anal., 2014, 90, 134-138.
[http://dx.doi.org/10.1016/j.jpba.2013.11.031] [PMID: 24366214]
[15]
Zhou, Y.F.; Chen, B.B.; Chen, J.Y.; Dong, Y.W.; Wang, S.H.; Wen, C.C.; Wang, X.Q.; Yu, X.M. determination and pharmacokinetic study of jaceosidin in rat plasma by UPLC-MS/MS. Acta Chromatogr., 2018, 30, 131-135.
[http://dx.doi.org/10.1556/1326.2017.00104]
[16]
Geng, P.W.; Zhang, J.; Chen, B.B.; Wang, Q.Q.; Wang, S.H.; Wen, C.C. Determination and pharmacokinetic study of dauricine in rat plasma by UPLC-MS/MS. Acta Chromatogr., 2018, 30, 136-140.
[http://dx.doi.org/10.1556/1326.2017.00118]
[17]
Ye, W.; Chen, R.; Sun, W.; Huang, C.; Lin, X.; Dong, Y.; Wen, C.; Wang, X. Determination and pharmacokinetics of engeletin in rat plasma by ultra-high performance liquid chromatography with tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1060, 144-149.
[http://dx.doi.org/10.1016/j.jchromb.2017.06.018] [PMID: 28622617]
[18]
Gullick, D.R.; Mott, K.B.; Bartlett, M.G. Chromatographic methods for the bioanalysis of pyrethroid pesticides. Biomed. Chromatogr., 2016, 30(5), 772-789.
[http://dx.doi.org/10.1002/bmc.3712] [PMID: 26916501]
[19]
Yang, X.; Ma, Y.; Li, N.; Cai, H.; Bartlett, M.G. Development of a method for the determination of Acyl-CoA compounds by liquid chromatography mass spectrometry to probe the metabolism of fatty acids. Anal. Chem., 2017, 89(1), 813-821.
[http://dx.doi.org/10.1021/acs.analchem.6b03623] [PMID: 27990799]
[20]
Zhong, Y.Y.; Luo, S.B.; Wang, L.; Wang, M.D.; Lin, X.; Yang, L.H.; Ye, F.M.; Chen, L.G. Sex-dependent pharmacokinetics of puerarin in rats after single oral administration. Lat. Am. J. Pharm., 2017, 36, 456-461.
[21]
Wang, Q.; Gao, X.M.; Chen, L.G.; Chen, W.H.; Jin, W.Q.; Ye, L.X.; Lin, G.Y.; Geng, P.W. Determination of astilbin in rat plasma and application to a pharmacokinetic Study by UPLC-MS/MS. Lat. Am. J. Pharm., 2017, 36, 2397-2402.
[22]
Chen, L.G.; Jiang, Y.Y.; Yu, Z.; Zhang, Z.G.; Lin, G.Y.; Wang, S.H.; Ye, J. Determining concentrations of loganin in plasma of rat by UPLC-MS/MS method: applications for a pharmacokinetic study. Lat. Am. J. Pharm., 2017, 36, 2374-2378.
[23]
Chen, L.; You, W.; Chen, D.; Cai, Y.; Wang, X.; Wen, C.; Wu, B. Pharmacokinetic interaction study of ketamine and rhynchophylline in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry., BioMed Res. Int., 2018, 2018, 6562309
[http://dx.doi.org/10.1155/2018/1578643] [PMID: 29951541]
[24]
Wang, S.; Wu, H.; Huang, X.; Geng, P.; Wen, C.; Ma, J.; Zhou, Y.; Wang, X. Determination of N-methylcytisine in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2015, 990, 118-124.
[http://dx.doi.org/10.1016/j.jchromb.2015.03.025] [PMID: 25864013]
[25]
Ma, J.; Wang, S.; Huang, X.; Geng, P.; Wen, C.; Zhou, Y.; Yu, L.; Wang, X. Validated UPLC-MS/MS method for determination of hordenine in rat plasma and its application to pharmacokinetic study. J. Pharm. Biomed. Anal., 2015, 111, 131-137.
[http://dx.doi.org/10.1016/j.jpba.2015.03.032] [PMID: 25880244]
[26]
Xiong, J.H.; Ye, H.; Lin, Y.X.; Yang, J.Z.; Chen, D.W.; Yu, D.G.; Chen, L.G. Determining concentrations of icotinib in plasma of rat by uplc method with ultraviolet detection: applications for pharmacokinetic studies. Curr. Pharm. Anal., 2017, 13, 340-344.
[http://dx.doi.org/10.2174/1573412912666160815115244]
[27]
Lin, Y.X.; Pan, P.P.; Chen, L.G.; Yang, J.Z.; Chen, D.W.; Wang, S.J.; Xiong, J.H. Simultaneous determination of doxofylline and its metabolite theophyl-line in rat plasma by ultra performance liquid chromatography. Curr. Pharm. Anal., 2016, 12, 296-299.
[http://dx.doi.org/10.2174/1573412912666151207190458]
[28]
Hou, S.Y.; Yang, S.L.; He, H.L.; Chen, Y.; Wang, J.H.; Wang, Y.; Chen, L.N. Multi-templates molecularly imprinted polymer for the specific solid-phase extraction of saponins from Panax notoginseng herbal extract. Curr. Pharm. Anal., 2015, 11, 292-299.
[http://dx.doi.org/10.2174/1573412911666150211002025]
[29]
Wang, J.; Zhao, T.; Kong, J.; Peng, H.; Lv, P.; Li, J.; Cao, X.; Zhang, S. Determination of vitacoxib, a novel COX-2 inhibitor, in equine plasma using UPLC-MS/MS detection: Development and validation of new methodology. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1061-1062, 270-274.
[http://dx.doi.org/10.1016/j.jchromb.2017.07.024] [PMID: 28759842]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 6
Year: 2020
Published on: 30 June, 2020
Page: [705 - 711]
Pages: 7
DOI: 10.2174/1573412915666190220101658
Price: $65

Article Metrics

PDF: 17
HTML: 1