盐酸坦洛新缓释胶囊在犬体内的药动学

目的建立犬血浆中坦洛新浓度的测定方法,并应用于盐酸坦洛新缓释胶囊中坦洛新犬体内的药动学研究。方法液相色谱-串联质谱法(LC-MS/MS)测定犬血浆中的坦洛新浓度。坦洛新血浆样品经乙酸乙酯萃取,Agilent ZORBAX SB-C18柱(150 mm×2.1 mm,5μm)分离,阿立哌唑为内标,流动相A为体积分数为0.1%的甲酸水溶液,B为乙腈,线性梯度洗脱,电喷雾电离源(ESI),以多反应离子监测(multiple reaction monitoring,MRM)方式进行正离子检测,用于分析的定量离子分别为m/z409→m/z228(坦洛新),m/z 447.5→m/z 284.8(内标:阿立哌唑)。结果犬血浆中坦洛新的线性为0.1～20.0μg.L-1,定量下限为0.1μg.L-1,日内和日间精密度(RSD)均小于13.59%,准确度(relative error,RE)为-2.54%～4.27%。结论本方法适用于盐酸坦洛新缓释胶囊在犬体内的药动学研究。

Pharmacokinetic study of tamsulosin hydrochloride sustained-release capsules in Beagle dogs

Objective To develop a method for the determination of tamsulosin in dog plasma and apply the method to evaluate the pharmacokinetics of tamsulosin in dog.Methods The plasma containing tamsulosin was extracted by liquid-liquid extraction and then the analyte and internal standard aripiprazole were separated on an Agilent ZORBAX SB-C18 column(150 mm×2.1 mm,5 μm)with a mobile phase of A-0.1%() formic acid solution,B-acetonitrile in a manner of linear gradient elution at a flow rate of 0.3 mL · min-1.Detection was performed on a triple quadrupole tandem mass spectrum by multiple reaction monitoring(MRM)mode using the electrospray ionization technique in positive mode.Quantitation analysis was performed using multiple reaction monitoring(MRM)of the transitions of m/z409→m/z228 for tamsulosin,m/z 447.5→m/z 284.8 for aripiprazole,respectively,with a scan time of 200 ms per transition.Results The method was linear over the concentration range of 0.1-20.0 μg · L-1.The lower limit of quantification(LLOQ)was 0.1 μg · L-1 in dog plasma with acceptable precision and accuracy.The intra-and inter-day precision was less than 13.59% determined from quality control(QC)samples at concentrations of 0.2,2.0 and 16.0 μg · L-1,and the accuracy was between-2.54% and 4.27%.Conclusions The method can be utilized for pharmacokinetic study of tamsolusin in dog plasma,which provide the advantage of sensitivity,specificity and simplicity.