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

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

Volume: 25 Issue: 14

Author(s): Kun Feng, Sherwin K. B. Sy, Mingming Yu, Zhihua Lv*Meixing Yan*

Affiliation:

• School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, PR China
• Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266003, PR China

• Women and Children Hospital, Qingdao University, Qingdao, 266034, China

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.

Cite this article as:

Feng Kun, Sy K. B. Sherwin, Yu Mingming, Lv Zhihua*, Yan Meixing*, Simultaneous Determination of Levo-tetrahydropalmatine and Naltrexone in Rat Plasma by LC-MS/MS and its Application in a Pharmacokinetic Study, Current Pharmaceutical Biotechnology 2024; 25 (14) . https://dx.doi.org/10.2174/0113892010271975231218074830