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DPP-4抑制剂LGT-6在不同种属血浆中蛋白结合率的比较
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| 篇名： | DPP-4抑制剂LGT-6在不同种属血浆中蛋白结合率的比较 |
| TITLE： | Comparison of Protein Binding Rate of DPP- 4 Inhibitor LGT- 6 in Different Species of Plasma |
| 摘要： | 目的：建立二肽基肽酶4抑制剂LGT-6在不同种属血浆中蛋白结合率的测定方法并比较差异。方法：采用平衡透析法，以磷酸盐缓冲液为透析外液，将3、30、300、3000nmol/L的LGT-6分别在大鼠、猴、人血浆（即透析内液）中平衡48h。以甲苯磺丁脲为内标，采用超高效液相色谱-串联质谱法测定透析内、外液中LGT-6的浓度，计算血浆蛋白结合率。以ACQUITYUPLCHSST3为色谱柱，以水（含0.01％甲酸）-乙腈（含0.01％甲酸）为流动相进行梯度洗脱，流速为0.6mL/min，柱温为40℃，进样量为2μL；离子源为电喷雾离子源，监测模式为多反应监测模式，采集模式为正离子模式，定量分析用离子对分别为m/z487.0→434.3（LGT-6）、m/z271.1→172.0（内标）。结果：在3、30、300、3000nmol/L浓度下，LGT-6在大鼠血浆中的蛋白结合率分别为（96.25±0.97）％、（84.16±1.24）％、（78.25±0.61）％、（66.63±0.95）％，在猴血浆中的蛋白结合率分别为（98.54±0.58）％、（87.27±1.01）％、（79.35±0.86）％、（66.69±0.54）％，在人血浆中的蛋白结合率分别为（99.40±1.03）％、（84.48±1.15）％、（77.62±0.77）％、（66.93±0.48）％。在相同浓度下，LGT-6在大鼠、猴和人血浆中的蛋白结合率没有明显差异（P＞0.05）；在相同种属血浆中，不同浓度LGT-6的血浆蛋白结合率组间比较差异有统计学意义（P＜0.05），且有随药物浓度的升高而降低的趋势。结论：成功建立了测定LGT-6血浆蛋白结合率的方法。在相同浓度下，LGT-6在大鼠、猴、人血浆中的蛋白结合率没有明显的种属差异，但有明显的浓度依赖趋势。 |
| ABSTRACT： | OBJECTIVE：To establish the method for determining protein binding rate of dipeptidyl peptidase- 4 inhibitor LGT- 6 in different species of plasma ，and to compare their difference. METHODS ：By equilibrium dialysis ，LGT-6（3，30，300，3 000 nmol/L）was equilibrated in rat ，monkey and human plasma （i. e. internal dialysis solution ）for 48 h，using phosphate buffer as the external dialysis solution. The concentration of LGT- 6 in internal and external dialysis solution was determined by UPLC-MS/MS using tolbutamide as internal standard ，and the plasma protein binding rate was calculated. The determination was performed on ACQUITY UPLC HSS T 3 column with water （containing 0.01％ formic acid ）-acetonitrile（containing 0.01％ formic acid ）as mobile phase at the flow rate of 0.6 mL/min. The column temperature was 40 ℃，and the sample size was 2 μL. The ion source was electrospray ion source ，and the multiple ion monitoring mode was used to carry out positive ionization scanning. The ion pairs for quantitative analysis were m/z 487.0→434.3（LGT-6），m/z 271.1→172.0（internal standard ），respectively. RESULTS ：At the concentrations of 3，30，300，and 3 000 nmol/L，the protein binding rates of LGT- 6 in rat plasma were （96.25±0.97）％，（84.16± 1.24）％，（78.25±0.61）％，（66.63±0.95）％；the protein protein binding rates in monkey plasma were （98.54±0.58）％，（87.27± 1.01）％，（79.35±0.86）％，（66.69±0.54）％；the protein binding rates in human plasma were （99.40±1.03）％，（84.48± 1.15）％，（77.62±0.77）％，（66.93±0.48）％. At the same concentration ，the protein binding rates of LGT- 6 in rat ，monkey and human plasma had no significant difference （P＞0.05）. In the same species of plasma ，there were significant differences in the plasma protein binding rates of different concentration of LGT-6 among those groups （P＜0.05），and it decreased with 才〔2016〕4015） the increase of drug concentration. CONCLUSIONS ： The method for the determination of plasma protein binding rate of LGT-6 is successfully established. The data revealed that the protein binding rate of LGT- 6 is concentration-dependent ， there was no obvious spec ies difference on protein binding rates of LGT- 6 in rat ，monkey and human plasma under the same concentration. |
| 期刊： | 2021年第32卷第14期 |
| 作者： | 廖伟科，杨华丽，王忠元，陈瑞，汤磊，崔杏，朱高峰 |
| AUTHORS： | LIAO Weike，YANG Huali，WANG Zhongyuan，CHEN Rui，TANG Lei，CUI Xing，ZHU Gaofeng |
| 关键字： | 二肽基肽酶4抑制剂；LGT-6；平衡透析法；超高效液相色谱-串联质谱法；血浆蛋白结合率；不同种属血浆 |
| KEYWORDS： | Dipeptidyl peptidase- 4 inhibitor；LGT-6；Balanced dialysis ；UPLC-MS/MS；Plasma protein binding rate ； |
| 阅读数： | 240 次 |
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