title: HPLC-APCI-MS for the determination of teprenone in human plasma: method and clinical application.
abstract: A sensitive high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method for the determination of teprenone (GGA) in human plasma using menatetrenone as the internal standard (I.S.) was established. After protein precipitation with ethanol, the plasma sample was extracted by cyclohexane and separated by high performance liquid chromatography on a reversed phase C8 HPLC column with a mobile phase of water-methanol (4:96, v/v). GGA was determined with atmospheric pressure chemical ionisation-mass spectrometry (APCI-MS). HPLC-APCI-MS was performed in the selected ion monitoring (SIM) mode using target ions at [M+H]+m/z 331.3 for GGA and [M+H]+m/z 445.4 for the I.S. Calibration curve was linear over the range of 0.3-1000 ng/ml. The lower limit of quantification was 0.3 ng/ml. The intra- and inter-batch variability values were less than 7.8% and 8.7%, respectively. The method was successfully applied in the pharmacokinetic study in which plasma concentrations of GGA in 20 healthy Chinese volunteers were determined up to 24 h after administration of capsule containing 50 mg GGA. The maximum GGA plasma concentration (Cmax) was 246.9+/-85.4 ng/ml, the elimination half-life (t1/2) was 3.38+/-1.20 h, and the time to the Cmax was 5.35+/-1.39 h.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, and Organization for State Drug Clinical Trial, The First Affiliated Hospital of Nanjing Medical University, China. dinglidl@hotmail.com
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Tian
authors.initials: T
authors.lastname: Zhu
authors.forename: Qinxin
authors.initials: Q
authors.lastname: Song
authors.forename: Yindi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Shen
mesh_terms: D000897:Anti-Ulcer Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001274:Atmospheric Pressure; D002138:Calibration; D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004224:Diterpenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D007477:Ions / Q000737:chemistry*; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D002214:Capsules; D004224:Diterpenes; D007477:Ions; C031049:geranylgeranylacetone