title: LC-ESI-MS/MS analysis and pharmacokinetics of heterophyllin B, a cyclic octapeptide from Pseudostellaria heterophylla in rat plasma.
abstract: Heterophyllin B (HB) is a cyclic octapeptide isolated from Pseudostellaria heterophylla. HB is used as the quality control index for evaluating P. heterophylla in the Chinese Pharmacopoeia. A rapid and sensitive LC-ESI-MS/MS method was developed and validated for the analysis of HB in rat plasma. Sample preparation consisted of a solid-phase extraction step for the removal of interference and preconcentration of the target analyte HB and the internal standard N-acetylcysteine before chromatographic analysis by MS/MS detection. The separation of HB and N-acetylcysteine was performed using a Hypersil GOLD™ C18 column and a mixture of methanol-water (60:40, v/v) containing 10 mmol/L ammonium formate and 0.1% formic acid as the mobile phase. The determination step was optimized in the selected reaction monitoring mode for the highly selective and sensitive quantitation of HB in rat plasma. Intra- and inter-assay precision (as relative standard deviation) was ≤9.1%, and accuracy was between 92.6 and 102.7%. The validated method was successfully applied to quantify HB concentrations up to 7 h after tail intravenous injections of 2.08, 4.16 and 8.32 mg/kg HB in rats. The LC-MS/MS method identified the relevant pharmacokinetic parameters of HB and its studied analog.
authors.affiliation: Cardiovascular Medicine, the First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Wai-Ou
authors.initials: WO
authors.lastname: Zhao
authors.affiliation: Emergency Department, the First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.affiliation: Emergency Department, the First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of General Surgery, the First Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D029748:Caryophyllaceae / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D010456:Peptides, Cyclic / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010456:Peptides, Cyclic; C000608358:heterophyllin B
keywords: LC-MS/MS; Pseudostellaria heterophylla; cyclic peptide; heterophyllin B; pharmacokinetics