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| 基于LC-MS/MS技术的罗库溴铵微透析探针回收率测定的方法学研究 |
| 王秀云1,方俊聪2,3,杨光2,3,许子华2,3,赵鑫2,3,范国荣1,2,3* |
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(1. 福建中医药大学药学院药物制剂教研室, 福州 350108;
2. 第二军医大学药学院药物分析学教研室, 上海 200433;
3. 上海市药物(中药)代谢产物研究重点实验室, 上海 200433
*通信作者) |
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| 摘要: |
| 目的 建立罗库溴铵微透析探针回收率的测定方法,考察罗库溴铵在体外及SD大鼠体内探针回收率的稳定性和重现性,为进一步体内微透析试验提供依据。方法 采用LC-MS/MS技术测定透析液中罗库溴铵浓度,计算相应的探针回收率;采用增量法(正透析法)和减量法(反透析法)考察不同流速(0.5、1.0、2.0、3.0、4.0 μL/min)、不同药物浓度(50、200、500 ng/mL)对体外探针回收率的影响。采用减量法测定SD大鼠体内的探针回收率,并与体外结果进行比较。结果 在相同条件下,探针体外回收率在流速为0.5~4 μL/min范围内随着流速增加而降低;同一流速下,探针回收率与罗库溴铵浓度无关;增量法和减量法所测得的体外探针回收率在相同条件近似相等,且稳定性良好。减量法测得的SD大鼠体内探针回收率结果与体外相近。结论 微透析技术可用于罗库溴铵体内药物动力学研究,反透析法可作为罗库溴铵体内研究的探针回收率测定方法。 |
| 关键词: 罗库溴铵 微透析 探针回收率 液相色谱-串联质谱法 |
| DOI：10.3724/SP.J.1008.2015.00396 |
| 投稿时间：2014-11-29修订日期：2014-12-26 |
| 基金项目:国家"重大新药创制"科技重大专项(2012ZX09103101-012). |
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| Method for determination of microdialysis probe recovery of rocuronium by LC-MS/MS |
| WANG Xiu-yun1,FANG Jun-cong2,3,YANG Guang2,3,XU Zi-hua2,3,ZHAO Xin2,3,FAN Guo-rong1,2,3* |
(1. Department of Pharmaceutics, School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, Fujian, China;
2. Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;
3. Shanghai Key Laboratory for Pharmaceutical (Chinese Materia Medica) Metabolite Research, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To establish a method for determining the recovery of rocuronium microdialysis probe by LC-MS/MS, so as to investigate the stability and reproducibility of microdialysis probe recovery during in vivo and in vitro microdialysis trials and to provide evidence for in vivo microdialysis. Methods The concentration of rocuronium in dialysate was determined by LC-MS/MS and the probe recovery was calculated.The effects of different drug concentrations (50, 200, and 500 ng/mL) and flow rates(0.5, 1.0, 2.0, 3.0, and 4.0 μL/min)on the probe recovery were determined by incremental (dialysis) and reduction (retrodialysis) methods. The in vivo probe recovery in SD rats was determined by reduction method, and its result was compared with that of the in vitro trial. Results The in vitro probe recovery decreased with the increase of flow rate within a range of 0.5-4 μL/min under the same condition. At the same flow rate, different concentrations of rocuronium had little influence on the probe recovery. Under the same condition, the in vitro recovery obtained by incremental and reduction methods were approximately equal and showed a good stability. The in vivo probe recovery obtained by reduction method was similar to the in vitro one. Conclusion Microdialysis can be used for pharmacokinetic study of rocuronium, and retrodialysis method can be used to study probe recovery of rocuronium in vivo. |
| Key words: rocuronium microdialysis probe recovery liquid chromatography tandem mass spectrometry |
