Comparison of fused-core and conventional particle size columns by LC-MS/MS and UV: Application to pharmacokinetic study
Comparison of fused-core and conventional particle size columns by LC-MS/MS and UV: Application to pharmacokinetic study
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DOI：
10.1016/j.jpba.2009.05.011
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发表时间：
2009-10-15
影响因子：
3.4
通讯作者：
Fast, Douglas M.
中科院分区：
文献类型：
--
作者：
Song, Wei;Pabbisetty, Deepthi;Fast, Douglas M.
采用大鼠血浆中两种药物的LC-MS/MS分析，比较了融合芯（表面多孔）高效液相色谱包装材料与常规全孔颗粒材料的色谱性能。两种市售抗抑郁药丙咪嗪和地西帕明使用传统的C（18）分析柱（5 μ m, 2.0 mm x 30 mm）和熔芯C（18）柱（2.7 μ m, 2.1 mm x 30 mm）进行检测。在相同的操作条件下，比较了保留时间、色谱柱效率、压降、分辨率和负载能力。融合核心柱的分析时间缩短34%，效率提高2-3倍(N)。柱上注入萃取液25 μ l时，加载能力LIP无峰值畸变。流速为1.0 ml/min的记录背压不超过3400 psi，使其与标准HPLC设备（通常额定为6000 psi）兼容。对两种流动相进行了检测，作为有机碱改性剂的啉比三乙胺的S/N提高了2-5倍，接近检测限。采用2.7 μ m熔芯柱对提取蛋白沉淀大鼠血浆中的丙咪嗪和去丙咪嗪进行LC-MS/MS分析。丙咪嗪和地西帕明在0.5 ~ 1000 ng/ml浓度范围内均呈线性。在三个QC水平上，运行内精密度（%CV）和准确度（%bias）在+/- 7.8%和+/- 7.3%范围内，在定量限水平上，两种分析物在14.7%和14.4%范围内。在单方法定性运行后，将该方法应用于口服丙咪嗪的雄性大鼠药代动力学研究样品的定量。(C) 2009 Elsevier B.V.版权所有
The chromatographic performance of fused-core (Superficially porous) HPLC packing materials was compared with conventional fully porous particle materials for LC-MS/MS analysis of two pharmaceuticals in rat plasma. Two commercially available antidepressants, imipramine and desipramine, were assayed using a conventional analytical C(18) column (5 mu m, 2.0 mm x 30 mm) and a fused-core C(18) column (2.7 mu m, 2.1 mm x 30 mm). Retention time, column efficiency, pressure drop, resolution, and loading capacity were compared under the same operating conditions. The fused-core column demonstrated reduced assay time by 34% and 2-3-fold increased efficiency (N). Loading capacity LIP to 25 mu l of extract injected on column showed no peak distortion. The registered back-pressure from a flow rate of 1.0 ml/min did not exceed 3400 psi making it compatible with standard HPLC equipment (typically rated to 6000 psi). Two mobile phases were examined, and morpholine as an organic base modifier yielded a 2-5-fold increase in S/N near the limit of detection over triethylamine. The 2.7 mu m fused-core column was applied to the analysis of imipramine and desipramine in extracted, protein precipitated rat plasma by LC-MS/MS. The calibration curves were linear in the concentration range of 0.5-1000 ng/ml for both imipramine and desipramine. Intra-run precisions (%CV) and accuracies (%bias) were within +/- 7.8% and +/- 7.3% at three QC levels and within 14.7% and 14.4% at the LOQ level for both analytes. Following a single method qualification run, the method was applied to the quantitation of pharmacokinetic study samples after oral administration of imipramine to male rats. (C) 2009 Elsevier B.V. All rights reserved.