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).
METHODS AND RESULTS:
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)).
CONCLUSIONS:
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. |
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