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

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