Matrine determination and pharmacokinetics in human plasma using LC/MS/MS

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Biomedical Science

Background:

• Matrine, a natural alkaloid, possesses various pharmacological properties.
• Accurate quantification of matrine in biological matrices is crucial for pharmacokinetic studies.
• Existing methods may lack the sensitivity or specificity required for clinical applications.

Purpose of the Study:

• To develop and validate a sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for matrine determination in human plasma.
• To apply the validated method in a clinical pharmacokinetic study following oral administration of matrine.

Main Methods:

• Plasma samples were extracted using isopropanol:ethyl acetate (5:95, v/v).
• Chromatographic separation was performed using a mobile phase of 5-mM ammonium acetate and acetonitrile (70:30, v/v) at a flow rate of 0.20 mL/min.
• Detection was achieved via positive-ion electrospray tandem mass spectrometry (LC/MS/MS) with huperzine A as the internal standard.

Main Results:

• The LC/MS/MS method demonstrated accuracy, specificity, and sensitivity for matrine quantification in human plasma over a concentration range of 5-2000 ng/mL.
• Pharmacokinetic analysis after single oral doses (100, 200, 400 mg) showed dose-proportional increases in the area under the curve (AUC(0-t)) and maximum concentration (C(max)).
• Matrine's half-life (t(1/2)) and time to maximum concentration (T(max)) were independent of the administered dose.

Conclusions:

• The developed LC/MS/MS method is suitable for the reliable quantification of matrine in human plasma.
• The pharmacokinetic profile of orally administered matrine exhibits dose-proportionality for key exposure parameters.
• Further research can utilize this validated method to explore matrine's therapeutic potential and optimize dosing regimens.