Simultaneous Determination of Levo-tetrahydropalmatine and Naltrexone in Rat Plasma by LC-MS/MS and its Application in a Pharmacokinetic Study


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Abstract

Background:Levo-tetrahydropalmatine and low-dose naltrexone are used in association with reducing cocaine-related cravings, but there are no analytical methods for the quantitative simultaneous analysis of this drug combination.

Objective:A highly selective and sensitive LC-MS/MS assay was developed and validated to simultaneously quantify l-THP and naltrexone. The analytical method for l-THP offers improved sensitivity compared to previously published methods.

Methods:The product ion transitions of l-THP and naltrexone were 357.0→193.0 and 342.2→324.1, respectively. Chromatographic separations were performed using a BEH-C18 column by an isocratic elution mode with acetonitrile and 0.1% formic acid in water containing 3 mM ammonium acetate. L-THP and naltrexone were extracted from rat plasma using a liquidliquid extraction method.

Results:For l-THP and naltrexone, the assay displayed good linear response over a concentration range of 0.5-1000 ng/mL and 0.25-500 ng/mL, respectively. The intra-day accuracy of the method for l-THP and naltrexone was 93.8-101% with a precision (%CV) of 2.43-8.15% and 93.4-108% with a precision of 3.47-8.22%. The inter-day accuracy for l-THP and naltrexone was 91.2-102% with a CV of 2.46–8.06% and 91.5–97.8% with a CV of 3.29–8.92%, respectively.

Conclusion:The assay has been used for pharmacokinetic studies of l-THP and naltrexone in the rat.

About the authors

Kun Feng

Women and Children Hospital, Qingdao University

Email: info@benthamscience.net

Sherwin Sy

Department of Statistics, State University of Maringá

Email: info@benthamscience.net

Mingming Yu

School of Medicine and Pharmacy, Ocean University of China

Email: info@benthamscience.net

Zhihua Lv

School of Medicine and Pharmacy, Ocean University of China

Author for correspondence.
Email: info@benthamscience.net

Meixing Yan

Women and Children Hospital, Qingdao University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Liu, X.; Yang, Z.; Li, R.; Xie, J.; Yin, Q.; Bloom, A.S.; Li, S.J. Responses of dopaminergic, serotonergic and noradrenergic networks to acute levo-tetrahydropalmatine administration in naïve rats detected at 9.4 T. Magn. Reson. Imaging, 2012, 30(2), 261-270. doi: 10.1016/j.mri.2011.09.006 PMID: 22079072
  2. Mantsch, J.R.; Wisniewski, S.; Vranjkovic, O.; Peters, C.; Becker, A.; Valentine, A.; Li, S.J.; Baker, D.A.; Yang, Z. Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats. Pharmacol. Biochem. Behav., 2010, 97(2), 310-316.
  3. Zhang, Z.; Jin, G.; Xu, S.; Yu, L.; Chen, Y.; Jiang, F.; Zhang, Y.; Sun, Z.; Ding, Y.; Bian, C. Effects of l-stepholidine on the central nervous and cardiovascular systems. Zhongguo yao li xue bao, 1986, 7(6), 522-526.
  4. Liu, J.; Dai, R.; Damiescu, R.; Efferth, T.; Lee, D.Y.W. Role of Levo-tetrahydropalmatine and its metabolites for management of chronic pain and opioid use disorders. Phytomedicine, 2021, 90, 153594. doi: 10.1016/j.phymed.2021.153594 PMID: 34144869
  5. Huang, Y.; Ma, Z.; Zheng, C.; Ma, X.K.; Taylor, D.H.; Gao, M.; Lukas, R.J.; Wu, J. Levo-tetrahydropalmatine inhibits α4β2 nicotinic receptor response to nicotine in cultured SH-EP1 cells. Acta Pharmacol. Sin., 2022, 43(4), 889-896. doi: 10.1038/s41401-021-00709-1 PMID: 34253876
  6. Xu, C.; Li, R.; Wu, J. Effects of Yuanhu-Zhitong tablets on alcohol-induced conditioned place preference in mice. Biomed. Pharmacother., 2021, 133, 110962. doi: 10.1016/j.biopha.2020.110962 PMID: 33166765
  7. Porter, S.J.; Somogyi, A.A.; White, J.M. Kinetics and inhibition of the formation of 6β‐naltrexol from naltrexone in human liver cytosol. Br. J. Clin. Pharmacol., 2000, 50(5), 465-471. doi: 10.1046/j.1365-2125.2000.00281.x PMID: 11069441
  8. Julius, D. NIDA’s naltrexone research program. NIDA Res. Monogr., 1976, 9(9), 5-11. PMID: 187943
  9. Tennant, F.S., Jr; Rawson, R.A.; Cohen, A.J.; Mann, A. Clinical experience with naltrexone in suburban opioid addicts. J. Clin. Psychiatry, 1984, 45(9 Pt 2), 42-45. PMID: 6469935
  10. Mannelli, P.; Patkar, A.A.; Peindl, K.; Gottheil, E.; Wu, L.T.; Gorelick, D.A. Early outcomes following low dose naltrexone enhancement of opioid detoxification. Am. J. Addict., 2009, 18(2), 109-116. doi: 10.1080/10550490902772785 PMID: 19283561
  11. Mannelli, P.; Peindl, K.; Patkar, A.A.; Wu, L.T.; Pae, C.U.; Gorelick, D.A. Reduced cannabis use after low-dose naltrexone addition to opioid detoxification. J. Clin. Psychopharmacol., 2010, 30(4), 476-478. doi: 10.1097/JCP.0b013e3181e5c168 PMID: 20631574
  12. Czoty, P.W.; Roberts, D.C.S. Thinking outside the synapse: pharmacokinetic-based medications for cocaine addiction. Neuropsychopharmacology, 2012, 37(5), 1079-1080. doi: 10.1038/npp.2011.269 PMID: 22071873
  13. Nestler, E.J. The Neurobiology of Cocaine Addiction Cocaine, 2013.
  14. Shorter, D.; Kosten, T.R. Novel pharmacotherapeutic treatments for cocaine addiction. BMC Med., 2011, 9(1), 119. doi: 10.1186/1741-7015-9-119 PMID: 22047090
  15. Sushchyk, S.; Xi, Z.X.; Wang, J.B. Combination of levo-tetrahydropalmatine and low dose naltrexone: A promising treatment for prevention of cocaine relapse. J. Pharmacol. Exp. Ther., 2016, 357(2), 248-257. doi: 10.1124/jpet.115.229542 PMID: 26903543
  16. Apostolidi, A.; Protopapa, C.; Siamidi, A.; Vlachou, M.; Dotsikas, Y. Dissolution assay of bupropion/naltrexone hydrochloride salts of bilayer composition tablets following the development and validation of a novel HPLC method. Materials , 2022, 15(23), 8451. doi: 10.3390/ma15238451 PMID: 36499947
  17. Alshogran, O.Y.; Zayed, A.L. A Simple HPLC-MS/MS method for quantification of naltrexone and 6-beta naltrexol: An application to effect of uremic toxins on metabolic reduction. J. Young Pharm., 2019, 11(3), 261-265. doi: 10.5530/jyp.2019.11.53
  18. Kabaweh, M.; Sakur, A.A. Determination of some bronchodilator and expectorant drugs (guaifenesin and theophylline) using HPLC technique. Res. J. Pharma. Technol., 2019, 12(4), 1915-1918. doi: 10.5958/0974-360X.2019.00320.2
  19. Wang, W.; Liu, J.; Zhao, X.; Peng, Y.; Wang, N.; Lee, D.Y.W.; Dai, R. Simultaneous determination of L ‐tetrahydropalmatine and its active metabolites in rat plasma by a sensitive ultra‐high‐performance liquid chromatography with tandem mass spectrometry method and its application in a pharmacokinetic study. Biomed. Chromatogr., 2017, 31(6), e3903. doi: 10.1002/bmc.3903 PMID: 27868218
  20. Abdallah, I.A.; Huang, P.; Liu, J.; Lee, D.Y.; Liu-Chen, L.Y.; Hassan, H.E. Development and validation of a high performance liquid chromatography quantification method of levo ‐tetrahydropalmatine and its metabolites in plasma and brain tissues: Application to a pharmacokinetic study. Biomed. Chromatogr., 2017, 31(4), e3850. doi: 10.1002/bmc.3850 PMID: 27606501
  21. Wu, X. Determination of levo-tetrahydropalmatine in rat plasma by HPLC and its application to pharmacokinetics studies. Afr. J. Pharm. Pharmacol., 2013, 7(10), 545-551. doi: 10.5897/AJPP12.843
  22. Chao-Wu, L.; Shuo, Z.; Hai-Qing, G.; Xiu-Mei, Z. Determination of l-tetrahydropalmatine in human plasma by HPLC and pharmacokinetics of its disintegrating tablets in healthy Chinese. Eur. J. Drug Metab. Pharmacokinet., 2011, 36(4), 257-262. doi: 10.1007/s13318-011-0045-x PMID: 21633914
  23. Yu, M.; Hassan, H.E.; Ibrahim, A.; Bauer, K.S.; Kelly, D.L.; Wang, J.B. Simultaneous determination of l-tetrahydropalmatine and cocaine in human plasma by simple UPLC–FLD method: Application in clinical studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 965(4), 39-44. doi: 10.1016/j.jchromb.2014.06.020 PMID: 24996068
  24. Duan, Y.; Zuo, Z.; Chen, Y.; Song, Q.; Yu, M.; Yang, Y. A validated LC-MS/MS method for the determination of L-hyoscyamine in human plasma: Application in clinical study. Biomedical Chromato., 2022, e5485.
  25. FDA. Guidance for Industry Bioanalytical Method Validation. 2018. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry
  26. Yu, M.; Abdallah, I.A.; Shin, S.H.; Hammell, D.C.; Stinchcomb, A.L.; Hassan, H.E. LC–MS determination of fentanyl in human serum and application to a fentanyl transdermal delivery pharmacokinetic study. Bioanalysis, 2017, 9(20), 1551-1560. doi: 10.4155/bio-2017-0174 PMID: 28914084
  27. Surendran, S.; Paul, D.; Sushmita, R.; Krishna, L.; Tiwari, N.K.; Giri, S.; Satheeshkumar, N. A validated LC–MS/MS method for the estimation of glimepiride and pitavastatin in rat plasma: Application to drug interaction studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1046, 218-225. doi: 10.1016/j.jchromb.2017.01.009 PMID: 28159531
  28. Feng, K.; Zhang, J.; Zhang, Y.; Jiang, T.; Lv, Z.; Yu, M. Simultaneous determination of FL118 and W34 in rat Blood by LC–MS/MS: Application to pharmacokinetic studies. Biomed. Chromatogr., 2020, 34(11), e4944. doi: 10.1002/bmc.4944 PMID: 32639034
  29. Zhu, S.; Zhang, J.; Lv, Z.; Yu, M. LC-MS/MS determination of apigenin in rat plasma and application to pharmacokinetic study. Curr. Pharm. Biotechnol., 2021, 22(2), 274-280. doi: 10.2174/1389201021666200807113144 PMID: 32767914

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