Rapid and sensitive determination of T J0711 hydrochloride,a novel vasodilatory β-blocker,in dog pla

来源 :2013年中国药物制剂大会——中国药学会药剂专业委员会2013年学术年会暨国际控释协会中国分会2013年学术年会 | 被引量 : 0次 | 上传用户:tting0226
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  A rapid, robust and sensitive ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed and validated for the quantitation of T J0711 hydrochloride (TJ0711 HC1), a novel vasodilatory β-blocker in dog plasma.The analyte and internal standard (IS, propranolol) were extracted from plasma by liquid-liquid extraction using ethyl acetate.Chromatographic separation was achieved on a Welch Ultimate-XB C18 column (2.1 × 100 mm, 3 μm) using isocratic elution with acetonitrile-2 mM ammonium formate (45∶55, v/v) at a flow rate of 0.3 mL/min.The MS/MS detection was carried out using electrospray ionization (ESI) in positive ion multiple reaction monitoring (MRM) mode through monitoring the ion transitions of m/z 376.2 → 252.2 and m/z 260.1 → 116.1 for TJ0711 HC1 and IS, respectively.The assay was fully validated with a dynamic range of 0.5-500 ng/ml (r > 0.999) and the lower limit of quantification was found to be 0.5 ng/mL.Moreover, the method had good accuracy (% Relative error ranging from-5.8% to 7.5%) and precision (% RSD < 7.8%).Extraction recoveries were consistent and were greater than 77% between the 4 quality control (QC) concentrations.No appreciable matrix effect was observed and the drug was sufficiently stable under all relevant analytical conditions.This method was successfully applied to preclinical pharmacokinetic studies in beagle dogs following intravenous administration of TJ0711 HC1.The preclinical pharmacokinetic results demonstrated linear pharmacokinetics of TJ0711 over the dose range from 0.03 to 0.3 mg/kg and no significant gender differences were observed in T J0711 plasma pharmacokinetic parameters.
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