title: Comparison of electron capture-atmospheric pressure chemical ionization and electrospray ionization for the analysis of gambogic acid and its main circulating metabolite in dog plasma.
abstract: Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi. Electron capture-atmospheric pressure chemical ionization (EC- APCI) and electrospray ionization (ESI) techniques, both in the negative ion mode, were evaluated regarding ionization, fragmentation patterns and sensitivity for simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of GA and its main circulating metabolite, 10-hydroxygambogic acid (10-OHGA) in dog plasma. Both analytes underwent extensive in-source fragmentation in EC-APCI, which was not desirable for reliable quantification of these analytes, whereas the substitution of ESI for EC-APCI almost eliminated the source instability of both analytes. Negative ion ESI was, therefore, chosen for the development of an LC-MS/MS method for simultaneous determination of these analytes. After protein precipitation by acetonitrile, all analytes were separated on a Luna C18 HST column (50 x 2.0 mm i.d., 2.5 microm) with a mobile phase of 20 mmol L(-1) ammonium acetate water solution containing 0.2% acetic acid:acetonitrile (18:82, v/v). The detection was performed on a tandem mass spectrometer using selective reaction monitoring mode. Calibration curves were linear over the range of 10-6000 ng mL(-1) for GA and 3-2000 ng mL(-1) for 10-OHGA. The method was successfully applied to the pharmacokinetics study of GA injection in six beagle dogs.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Linlin
authors.initials: L
authors.lastname: Hu
authors.forename: Shaohong
authors.initials: S
authors.lastname: Jin
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Qidong
authors.initials: Q
authors.lastname: Yu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000097:Acetonitriles; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs / Q000097:blood*; D005260:Female; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D013696:Temperature; D044004:Xanthones / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: C550001:10-hydroxygambogic acid; D000097:Acetonitriles; D044004:Xanthones; C052659:gambogic acid; C032159:acetonitrile