Wang Hairong, Zhang Lantong, Wang Qiao, Yuan Zhifang, Li Min
Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2006 May 1;835(1-2):71-6. doi: 10.1016/j.jchromb.2006.03.012. Epub 2006 Mar 29.
A sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed to determine m-nisoldipine in rat plasma. Sample was pretreated by a single-step protein precipitation with acetonitrile, in contrast to the liquid-liquid procedure frequently used for the extraction of 1,4-dihydropyridines from biologic samples. Separation of analyte and internal standard (I.S.) was performed on a Symmetry RP-C(18) analytic column (50 mm x 4.6 mm, 3.5 microm) with a mobile phase consisting of acetonitrile-water (80:20, v/v) at a flow rate of 0.5 ml/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) scan mode using TurboIonSpray ionization (ESI) source. The method was sensitive with a lower limit of quantification (LLOQ) of 0.2 ng/mL, with good linearity (r>or=0.9982) over the linear range of 0.2-20 ng/mL. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was successfully applied to pharmacokinetic and relative bioavailability studies of m-nisoldipine polymorphs in rats.
已开发出一种灵敏且特异的液相色谱-串联质谱（LC-MS-MS）法来测定大鼠血浆中的间尼索地平。与常用于从生物样品中提取1,4-二氢吡啶的液-液萃取法不同，样品采用乙腈一步蛋白沉淀法进行预处理。在Symmetry RP-C(18)分析柱（50 mm×4.6 mm，3.5 µm）上进行分析物和内标（I.S.）的分离，流动相为乙腈-水（80:20，v/v），流速为0.5 ml/min。API 4000三重四极杆质谱仪采用TurboIonSpray电离（ESI）源，在多反应监测（MRM）扫描模式下运行。该方法灵敏，定量下限（LLOQ）为0.2 ng/mL，在0.2 - 20 ng/mL的线性范围内具有良好的线性（r≥0.9982）。所有验证数据，如准确度、精密度和日间重复性，均在规定范围内。该方法已成功应用于大鼠中间尼索地平多晶型物的药代动力学和相对生物利用度研究。
