The aim of this study is to develop and validate a rapid, high-selective and sensitive supercritical fluid chromatography/tandem mass spectrometry (SFC–MS/MS) with a multiple reactions monitoring (MRM) mode method for the detection of ezetimibe in dog plasma. Several conditions were optimized systematically as follows: lipid–lipid extraction (LLE) performances were used to extract analytes from dog plasma; an ACQUITY HSS C₁₈ SB (1.8 μm, 3.0 × 100 mm) column was employed to separate the target compounds; the triple-quadrupole mass spectrometry equipped with electrospray ionization (ESI) source was applied to detect ezetimibe. The method, which required a relatively small volume of plasma (100 μL), was obtained at concentration ranging from 1.0 to 100 ng/mL(r² > 0.99). The lower limit of quantification (LLOQ)for ezetimibe was found to be as low as 1.0 ng/mL. In addition, the validations of the methodology including sensitivity, recovery, matrix effect, intra- and inter-day precision, accuracy and stability were all within acceptable limits. The C_max, AUC_0–inf and T_max values obtained in our study were 52.2 ± 6.3, 820.6 ± 4.3 and 1.25 ± 0.35 for reference formulation; 61.8 ± 12.6, 924.2 ± 4.7 and 2.00 ± 0 for test formulation. In conclusion, the method developed in this study can be successfully applied to pharmacokinetic studies after oral administration of ezetimibe in dogs.

这项研究的目的是开发和验证一种快速，高选择性和灵敏的超临界流体色谱/串联质谱法（SFC–MS / MS），该方法采用多反应监测（MRM）模式检测狗血浆中的依泽替米贝。 。系统优化了几个条件，如下所示：使用脂质-脂质提取（LLE）性能从狗血浆中提取分析物。使用ACQUITY HSS C ₁₈ SB（1.8μm，3.0×100 mm）色谱柱分离目标化合物；配备电喷雾电离（ESI）源的三重四极杆质谱仪用于检测依泽替米贝。该方法所需的血浆体积相对较小（100μL），浓度范围为1.0至100 ng / mL（r ² > 0.99）。依泽替米贝的定量下限（LLOQ）低至1.0 ng / mL。此外，包括灵敏度，回收率，基质效应，日内和日间精度，准确性和稳定性在内的方法学验证均在可接受的范围内。在我们的研究中，参考制剂的C _max，AUC _0-inf和T _max值分别为52.2±6.3、820.6±4.3和1.25±0.35。测试配方为61.8±12.6、924.2±4.7和2.00±0。总之，本研究中开发的方法可在狗中口服依泽替米贝后成功地用于药代动力学研究。