大鼠血浆中活性寡肽RX 31的HPLC-MS/MS定量分析方法研究  

Determination of active oligo-peptide RX 31 in rat plasma by HPLC-MS/MS method

作　　者：葛华[1,2] 向慎思[2,3] 王清清[2] 贾彦波[2] 宋海峰[2] 王东援[1] 

机构地区：[1]沈阳药科大学分析化学教研室,沈阳110016 [2]军事医学科学院放射与辐射医学研究所药理毒理研究室,北京100850 [3]南京军区南京总医院药品科,南京210002

出　　处：《军事医学科学院院刊》2010年第3期206-209,共4页Bulletin of the Academy of Military Medical Sciences

基　　金：国家高技术研究发展计划(863计划)重大专项(2003AA2Z347B);国家“重大新药创制”科技重大专项(2009ZX09304-004)

摘　　要：目的建立快速、灵敏的液相色谱-串联质谱法(HPLC-MS/MS)测定大鼠血浆中活性寡肽RX31的浓度。方法血浆样品经甲醇蛋白沉淀后,以0.1%甲酸-甲醇为流动相梯度洗脱,CapcellMGⅢCl8柱分离。采用电喷雾电离源,以多反应监测(MRM)方式进行正离子检测,用于定量分析的离子反应分别为m/z640.3→m/z623.3(RX31)和m/z596.1→m/z287.1(内标,RX20)。结果在本实验条件下,血浆中RX31的线性范围为3.91～500ng/ml,定量下限为3.91ng/ml,日内、日间精密度(相对标准差,RSD)均小于12%,准确度(相对误差,RE)在-11%～5%。结论该法快速、灵敏、准确,可用于RX31的药代动力学研究。Objective To develope a high performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）method for determination of active oligo-peptide RX 31 in rat plasma.Methods Rat plasma samples were precipitated with methanol.Chromatographic separation was performed on a Capcell MGⅢC18 column with the mobile phase consisting of 0.1% formic acid-methanol in the gradient elution mode at a flow-rate of 0.2 ml/min.A tandem mass spectrometer equipped with an electrospray ionization source was used as detector and operated in the positive ion mode.Quantification was performed using multiple reaction monitoring（MRM）with the precursor product combination ions of m/z 640.3→623.3 and m/z 596.1→287.1 for RX 31 and the internal standard（RX 20）,respectively.Results The linear calibration curve was obtained in the concentration range of 3.91-500 ng/ml.The lower limit of quantification was 3.91 ng/ml.The intra-and inter-day relative standard deviation over the entire concentration range was less than 12%.The accuracy ranged from-11% to 5% in terms of relative errors.Conclusion The method validation results showed that this method is rapid,sensitive,accurate,and applicable to the pharmacokinetic study of RX 31.[

关 键 词：寡肽类 色谱法 高压液相 光谱法 质量 电喷雾电离 血浆 药代动力学 

分 类 号：R96[医药卫生—药理学]