Objective:

2

To investigate

in vivo

and

in vitro

metabolites of coptisine and their metabolic pathways.

Method:

2

SD rats were given coptisine by single gavage (dose of 25 mg·kg

-1

). Urine and feces from 0 h to 48 h

bile from 0 h to 24 h

and plasma and brain tissue samples at 0.25

1

2 h after administration were collected.

In vitro

metabolism was incubated with rat liver microsomes and intestinal flora.The metabolites were analyzed and identified by the high-resolution HPLC-MS/MS technique.The liquid chromatography separation was carried out on ZORBAX SB-C

18

column (4.6 mm×150 mm

5 μm) with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution

the flow rate was 1.0 mL·min

-1

and column temperature was 25 ℃.The mass spectra were obtained in positive and negative ion mode with electrospray ionization (ESI)

the scanning range was

m

/

z

50-1 200.The relative molecular weight was determined according to the quasi-molecular ion peaks.The structures of metabolites were elucidated by comparing the data with literature data

including main ion peaks

UV spectrum and HPLC retention time information.

Result:

2

A total of 17 metabolites were identified in each sample

including 11 phase Ⅰ metabolites and 6 phase Ⅱ metabolites.The pathways to these metabolites were hydroxylation

demethylation

dehydrogenation

sulfation and glucuronide conjugation.

Conclusion:

2

Coptisine can produce metabolic reaction of phase Ⅰ and phase Ⅱ in rat

and metabolites are predominantly present in urine

and the main metabolic site is liver.Coptisine is poorly absorbed and rarely metabolized in gastrointestinal tract

so it is mostly excreted through feces by prototype.This experiment can provide material basis for the pharmacodynamics and pharmacology of coptisine.