Pharmacokinetic Study of Deltaline in Mouse Blood Based on UPLCMS/ MS

Author(s): Huanchun Song, Yiwei Huang, Dongqing Zhu, Shuhua Tong, Meiling Zhang, Xianqin Wang*, Xi Bao*.

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 2 , 2019

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Abstract:

Introduction: Deltaline, an aconitine-type alkaloid, was detected in mouse blood using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, and the pharmacokinetics of deltaline following intravenous administration in mice was studied.

Materials and Methods: The gelsenicine was used as the internal standard (IS). Deltaline and IS were eluted at a flow rate of 0.4 ml/min and separated on a UPLC BEH C18 column by gradient elution using acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) as a mobile phase. The following transitions were obtained at m/z 508.2→75.0 for deltaline and m/z 327.1→107.8 for gelsenicine in multiple reactions monitoring mode. Acetonitrile was used to precipitate protein. Six mice after intravenous administration of a single dose of deltaline (1 mg/kg), 20-µL blood samples from each mouse were collected from the tail vein.

Results: The UPLC-MS/MS method was sensitive and linear (r>0.995) with a lower limit of quantitation (LLOQ) of 0.1 ng/mL over the range of 0.1-500 ng/mL. Intra- and inter-day precisions were below 13%, the accuracy range was between 88.0% and 108.2%, the recovery was higher than 90.1%, and the matrix effect was between 102.9% and 108.1%.

Conclusion: The method was sensitive, fast, specific, and has been successfully applied to a pharmacokinetic study of deltaline after intravenous administration.

Keywords: Deltaline, pharmacokinetics, mouse, UPLC-MS/MS, blood, aconitine-type alkaloid.

[1]
Tong, P.; Xu, S.; Cao, G.; Jin, W.; Guo, Y.; Cheng, Y.; Jin, H.; Shan, L.; Xiao, L. Chondroprotective activity of a detoxicated traditional Chinese medicine (Fuzi) of Aconitum carmichaeli Debx against severe-stage osteoarthritis model induced by mono-iodoacetate. J. Ethnopharmacol., 2014, 151, 740-744.
[2]
Tong, P.; Wu, C.; Wang, X.; Hu, H.; Jin, H.; Li, C.; Zhu, Y.; Shan, L.; Xiao, L. Development and assessment of a complete-detoxication strategy for Fuzi (lateral root of Aconitum carmichaeli) and its application in rheumatoid arthritis therapy. J. Ethnopharmacol., 2013, 146, 562-571.
[3]
Wu, J.J.; Guo, Z.Z.; Zhu, Y.F.; Huang, Z.J.; Gong, X.; Li, Y.H.; Son, W.J.; Li, X.Y.; Lou, Y.M.; Zhu, L.J.; Lu, L.L.; Liu, Z.Q.; Liu, L. A systematic review of pharmacokinetic studies on herbal drug Fuzi: Implications for Fuzi as personalized medicine. Phytomedicine, 2018, 44, 187-203.
[4]
Wang, X.Q.; Song, Q.; Guo, X.Q.; Yan, J. Deltaline from Delphinium delavayi Franch. Acta Crystallogr. Sect. E Struct. Rep. Online, 2011, 67, 439.
[5]
Green, B.T.; Welch, K.D.; Gardner, D.R.; Stegelmeier, B.L.; Davis, T.Z.; Cook, D.; Lee, S.T.; Pfister, J.A.; Panter, K.E. Serum elimination profiles of methyllycaconitine and deltaline in cattle following oral administration of larkspur (Delphinium barbeyi). Am. J. Vet. Res., 2009, 70, 926-931.
[6]
Zou, C.L.; Liu, X.Y.; Wang, F.P.; Chen, Q.H. Two novel skeletal rearrangements involving in the C ring of C19-diterpenoid alkaloid deltaline derivatives. Chem. Pharm. Bull. (Tokyo), 2008, 56, 250-253.
[7]
Welch, K.D.; Gardner, D.R.; Stonecipher, C.A.; Green, B.T.; Pfister, J.A. Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats. Toxicon, 2017, 133, 91-94.
[8]
Welch, K.D.; Gardner, D.R.; Green, B.T.; Stonecipher, C.A.; Cook, D.; Pfister, J.A. Comparison of the serum toxicokinetics of larkspur toxins in cattle, sheep and goats. Toxicon, 2016, 119, 270-273.
[9]
Welch, K.D.; Green, B.T.; Gardner, D.R.; Cook, D.; Pfister, J.A. The effect of administering multiple doses of tall larkspur (Delphinium barbeyi) to cattle. J. Anim. Sci., 2015, 93, 4181-4188.
[10]
Green, B.T.; Welch, K.D.; Gardner, D.R.; Stegelmeier, B.L.; Pfister, J.A.; Cook, D.; Davis, T.Z. A toxicokinetic comparison of norditerpenoid alkaloids from Delphinium barbeyi and D. glaucescens in cattle. J. Appl. Toxicol., 2011, 31, 20-26.
[11]
Geng, P.; Luo, J.; Weng, Z.; Fan, Z.; Zhang, B.; Ma, J.; Wang, X.; Zhang, M. Determination of armepavine in mice blood by UPLC-MS/MS and its application to pharmacokinetic study. Biomed. Chromatogr., 2018, 32, e4273.
[12]
Wu, H.; Yan, Q.; Fan, Z.; Huang, M.; He, J.; Ma, J.; Wang, X. Determination of corypalmine in mouse blood by UPLC-MS/MS and its application to a pharmacokinetic study. Biomed. Chromatogr., 2018, 32, e4255.
[13]
Ma, J.; Wang, S.; Zhang, M.; Zhang, Q.; Zhou, Y.; Lin, C.; Lin, G.; Wang, X. Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma by UPLC-MS/MS and its application to cytochrome P450 activity study in rats. Biomed. Chromatogr., 2015, 29, 1203-1212.
[14]
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.
[15]
Wang, X.Q.; Wang, S.H.; Ma, J.S.; Ye, T.; Lu, M.; Fan, M.; Deng, M.J.; Hu, L.F.; Gao, Z. Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS. J. Pharm. Biomed. Anal., 2015, 115, 368-374.
[16]
Wang, S.H.; Wu, H.Y.; Huang, X.L.; Geng, P.W.; Wen, C.C.; Ma, J.S.; Zhou, Y.F.; Wang, X.Q. 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.
[17]
Zhang, Q.W.; Wen, C.C.; Xiang, Z.; Ma, J.S.; Wang, X.Q. 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.
[18]
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.
[19]
Pang, H.Q.; Tang, Y.P.; Cao, Y.J.; Tan, Y.J.; Jin, Y.; Shi, X.Q.; Huang, S.L.; Sun, D.Z.; Sun, J.; Tang, Z.S.; Duan, J.A. Comparatively evaluating the pharmacokinetic of fifteen constituents in normal and blood deficiency rats after oral administration of Xin-Sheng-Hua Granule by UPLC-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1061-1062, 372-381.
[20]
Zhang, X.; Liu, S.; Pi, Z.; Liu, Z.; Song, F. Simultaneous quantification method for comparative pharmacokinetics studies of two major metabolites from geniposide and genipin by online mircrodialysis-UPLC-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1041-1042, 11-18.
[21]
Wang, S.H.; Lin, Z.X.; Su, K.; Zhang, J.; Zhang, L.J.; Gao, Z.M.; Wang, Z.Y.; Ma, J.S.; Wang, X.Q. Effect of curcumin and pirfenidone on toxicokinetics of paraquat in rat by UPLC-MS/MS. Acta Chromatogr., 2018, 30, 26-30.
[22]
Fang, B.M.; Bao, S.H.; Wang, S.H.; Chen, M.L.; Chen, B.B.; Su, K.; Wen, C.C.; Zhou, Y.F.; Wang, X.Q.; Jin, Y.P. Pharmacokinetic study of ardisiacrispin A in rat plasma after intravenous administration by UPLC-MS/MS. Biomed. Chromatogr., 2017, 31, e3826.
[23]
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.
[24]
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.
[25]
Wang, W.; Zheng, X.; Wang, H.; Wang, L.; Jiang, J.; Hu, P. Development of an UPLC-MS/MS method for quantification of Avitinib (AC0010) and its five metabolites in human cerebrospinal fluid: Application to a study of the blood-brain barrier penetration rate of non-small cell lung cancer patients. J. Pharm. Biomed. Anal., 2017, 139, 205-214.
[26]
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.
[27]
Jin, Y.W.; Rao, Z.; Zhou, Y.; Zhang, G.Q.; Ma, Y.R.; Wang, X.D.; Shi, A.X.; Wu, X.A. Development of a LC-MS/MS method for simultaneous determination of bile acids and their conjugates in hepatocytes, tissue and fluids in rat. Curr. Pharm. Anal., 2018, 14, 331-341.
[28]
Jiang, Y.; Zhou, H.; Su, K.; Xu, M.Z.; Chen, B.B.; Chen, D.X.; Wen, C.C.; Wu, B.; Luo, X.H.; Wang, X.Q. Tissue distribution model of tramadol in rats by LC-MS. Lat. Am. J. Pharm., 2016, 35, 2261-2266.
[29]
Ma, J.S.; Zhang, Y.Q.; Zhang, M.L.; Fan, X.F.; Wang, Z.B.; Shentu, Y.P.; Wang, Z.Y.; Wang, X.Q. Determination of troxerutin in rabbit plasma by LC-ESI-MS and its application to a pharmacokinetic study. Lat. Am. J. Pharm., 2011, 30, 613-618.
[30]
Lin, G.Y.; Zhang, H.Y.; Xue, F.; Li, W.J.; Liu, N.H.; Chen, L.G.; Wang, X.Q.; Xu, R.N.; Ma, J.S. Determination of meropenem in rabbit plasma by LC-MS/MS. Lat. Am. J. Pharm., 2011, 30, 1895-1900.
[31]
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.
[32]
Gullick, D.R.; Mott, K.B.; Bartlett, M.G. Chromatographic methods for the bioanalysis of pyrethroid pesticides. Biomed. Chromatogr., 2016, 30, 772-789.
[33]
Yang, X.K.; Ma, Y.J.; Li, N.; Cai, H.J.; 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, 813-821.
[34]
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.
[35]
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.
[36]
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.


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Article Details

VOLUME: 15
ISSUE: 2
Year: 2019
Page: [194 - 199]
Pages: 6
DOI: 10.2174/1573412914666181011124515
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