四种前处理方法对LC-MS/MS测定大鼠血浆中复方鹿角颗粒多种成分基质效应的影响

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目的采用液相色谱-串联质谱法(LC-MS/MS)定量分析大鼠血浆中复方鹿角颗粒14种主要成分(补骨脂素、异补骨脂素、马钱苷、淫羊藿苷、柚皮苷、橙皮苷、朝藿定A、朝藿定B、朝藿定C、宝藿苷Ⅰ、红景天苷、特女贞苷、淫羊藿次苷Ⅱ、女贞苷),比较四种不同前处理方法的基质效应对其影响,并结合成分提取回收率选择适合的前处理方法。方法在大鼠空白血浆中加入低、中、高三种不同质量浓度的对照品溶液作为模拟血浆样品,瑞格列奈和地塞米松对照品分别为正、负离子内标。采用蛋白沉淀、液-液萃取、固相萃取和微固相萃取四种前处理方法,对最终测定的基质效应和提取回收率进行评价。结果采用微固相萃取法对大鼠血浆中复方鹿角颗粒14种主要成分高、中、低三种质量浓度的样品处理分析后,除橙皮苷、特女贞苷和中浓度女贞苷外,其余水平浓度样品的基质效应均在80%~120%范围间;除宝藿苷I和朝藿定A外,样品提取回收率均在70%以上。结论四种前处理方法中,采用微固相萃取法,样品基质效应对测定方法影响小,提取回收率高,操作简便、快速、灵敏度高、稳定性好,可以作为复方鹿角颗粒中14种主要成分在大鼠体内血药浓度测定和药代动力学研究的样品前处理方法。 OBJECTIVE To quantitatively analyze 14 main components of compound antler particle in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS / MS) (psoralen, isopsoralen, loganin, icariin, Naringin, hesperidin, attapulgine A, epimedin B, epimedin C, treasure glycoside I, salidroside, special virginia glycosides, Epimedium Ⅱ, virginia glycosides) The effects of matrix effects of four different pretreatment methods were compared, and the suitable pretreatment methods were selected according to the extraction recovery rate. Methods The blank, middle and high quality control solutions were added into the blank plasma of rats as simulated plasma samples. The standard of repaglinide and dexamethasone were positive and negative internal standard respectively. Four pretreatment methods: protein precipitation, liquid-liquid extraction, solid-phase extraction and micro-solid phase extraction, were used to evaluate the matrix effect and extraction recovery of the final determination. Results After micro-solid-phase extraction method was used to analyze the samples of 14 kinds of main components of the compound antler particle in rat plasma with three kinds of high, medium and low concentration of quality samples, except hesperidin, . The matrix effects of the other samples with the same concentration ranged from 80% to 120%. The recovery rates of samples were above 70% except for the addition of treasurein I and epimedin A. Conclusion The four pretreatment methods, micro-solid phase extraction method, the sample matrix effect on the determination of small, high recovery rate, easy to operate, fast, high sensitivity and good stability, can be used as the compound antler particle 14 kinds of main Composition pretreatment in rat plasma concentration determination and pharmacokinetic studies.
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