Pharmacokinetic study of lappaconitine hydrobromide in mice by LC-MS.
- Author:
Qing WANG
1
;
Zi-jing LI
;
Lu SUN
;
Li-ying GAO
;
Ming-hui LI
;
Jia-jia HAO
;
Xin ZHANG
;
Yu-ming SUN
Author Information
1. School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, China.
- Publication Type:Journal Article
- MeSH:
Aconitine;
administration & dosage;
analogs & derivatives;
chemistry;
pharmacokinetics;
Analgesics, Non-Narcotic;
administration & dosage;
chemistry;
pharmacokinetics;
Animals;
Area Under Curve;
Chromatography, Liquid;
methods;
Injections, Intravenous;
Male;
Mice;
Molecular Structure;
Spectrometry, Mass, Electrospray Ionization;
methods
- From:
Acta Pharmaceutica Sinica
2011;46(4):432-437
- CountryChina
- Language:English
-
Abstract:
A high sensitive and rapid method was developed for the analysis of lappaconitine in mouse plasma using liquid chromatography coupled to mass spectrometry (LC-MS). Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 585 --> m/z 535 and m/z 356 --> m/z 192, for the quantification of lappaconitine and tetrahydropalmatine (internal standard, IS), respectively. The method was linear over the concentration range of 3.0-2000.0 ng x mL(-1). The lower limit of quantification was 3.0 ng x mL(-1). Intra- and inter-run precisions (RSD) were both less than 9.9% and accuracy (RE) within +/- 4.8%. After single intravenous injections of lappaconitine hydrobromide at 1.0, 2.0 and 4.0 mg x kg(-1), the elimination half-lives (t(1/2)) were 0.47, 0.48 and 0.49 h, and the areas under the curve (AUC(0-t)) were 55.5, 110.5 and 402.9 ng x h x mL(-1), separately. The pharmacokinetic profile of lappaconitine was linear at relatively lower dose levels (1.0-2.0 mg x kg(-1)). When the dose increased farther to 4.0 mg x kg(-1), the Vz and CL decreased, and the increase fold of the AUC was much larger than that of the dose.
