title: Liquid chromatography-mass spectrometry method for determination of tetramethylpyrazine and its metabolite in dog plasma.
abstract: A liquid chromatography-mass spectrometry method is described for the determination of tetramethylpyrazine (TMP) and its active metabolite, 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) in dog plasma. This method involves a plasma clean-up step using protein precipitation procedure followed by LC separation and positive electrospray ionization mass spectrometry detection (ESI-MS). Chromatographic separation of the analytes was achieved on a C18 column using a mobile phase of methanol, water and acetic acid (50:50:0.6, v/v/v) at a flow rate of 1.0 ml/min. Selected ion monitoring (SIM) mode was used for analyte quantitation at m/z 137.2 for TMP, m/z 153.2 for HTMP and m/z 195.2 for caffeine. The linearity was obtained over the concentration ranges of 20-6000 ng/ml for TMP and 20-4000 ng/ml for HTMP and the lower limit of quantitation was 20 ng/ml for both analytes. For each level of QC samples, both inter- and intra-day precisions (R.S.D.) were <or=7.4% for TMP and <or=6.0% for HTMP, and accuracy (R.E.) was +/-6.0% for TMP and <or=3.5% for HTMP. The proposed LC-MS method was successfully applied to the pharmacokinetic studies of a TMP formulation preparation after oral administration to beagle dogs.
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Meiling
authors.initials: M
authors.lastname: Qi
authors.forename: Lin
authors.initials: L
authors.lastname: Fang
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D011719:Pyrazines / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D011719:Pyrazines; C017953:tetramethylpyrazine