Objective:To develop a LC-MS/MS method for simultaneous determination of jatrorrhizine

coptisine

palmatine and berberine in rat plasma. Method: Taking ACQUITY UPLC BEH C18column(2.1 mm×50 mm

1.7 μm) with mobile phase of acetonitrile-water (2 mmoL ammonium acetate and 0.05% formic acid)

flow rate was 0.3 mL·min-1

column temperature was 30 ℃.Strychnine was adopted as the internal standard

plasma samples were pretreated by protein precipitation with 4 times the amount of acetonitrile

electrospray ionization(ESI) was applied and operated in positive ionmode

quantification was performed by multiple reaction monitoring(MRM) of jatrorrhizine m/z 338.227→m/z 322.824

coptisine m/z 320.244→m/z 291.996

palmatine m/z 352.243→m/z 308.016

berberine m/z 336.227→m/z 277.981 and the internal standard m/z 335.264→m/z 184.017

respectively. Result: Calibration curve of jatrorrhizine

coptisine

palmatine and berberine in plasma were linear in the range of 1.01-505

1.06-530

1.13-565

1.07-535 μg·L-1;Lower limit of quantitation were 0.539 2

0.646 3

0.761 5 and 0.197 1 μg·L-1

respectively;Average recoveries were in order of 103.90%

101.50%

101.58% and 115.54%

respectively.RSD of intra-and inter-day

stability were less than 10%. Conclusion: This assay method was accurate

sensitive

specific and suitable for simultaneous determination and pharmacokinetic study of jatrorrhizine

coptisine

palmatine and berberine in rat plasma.