利塞膦酸钠皮肤微透析方法的建立

Establishment of Skin Microdialysis Method for Risedronate Sodium

目的建立利塞膦酸钠皮肤微透析方法。方法以利塞膦酸钠探针体外回收率为指标,采用增量法确定微透析试验中利塞膦酸钠的灌流速度及取样间隔;采用增量法和减量法考察灌流液流速及质量浓度对探针体外回收率和损失率的影响,以验证反透析法用于探针体内回收率测定的可行性。结果利塞膦酸钠探针体外回收率随流速的升高呈类线性下降。综合考虑试验因素,确定灌流速度为1.0μL/min,每次采样间隔为40 min,此条件下利塞膦酸钠的探针体外回收率为(45.85±0.63)%。在相同流速及温度下,不同质量浓度的利塞膦酸钠探针体外回收率变化不明显,且探针体外增量法回收率与减量法损失率相当(RSD=1.82%)。结论建立的利塞膦酸钠皮肤微透析方法可用于利塞膦酸钠经皮局部药效动力学研究。

Objective To establish a skin microdialysis method for risedronate sodium.Methods With the recovery rate of risedronate sodium as the index,the incremental method was used to determine the flow rate of perfusion fluid and sampling interval of risedronate sodium.The incremental method and decrement method were used to investigate the effect of flow rates and mass concentrations of perfusion fluid on the recovery rates and loss rates of the probe in vitro,so as to verify the feasibility of the reverse dialysis method applied to the determination of in vivo recovery rates of the probe.Results The in vitro recovery rates of risedronate sodium showed a similar linear decline trend with the increase of the flow rate.Combined with the comprehensive experimental factors,the flow rate of perfusion fluid was determined to be 1.0μL/min and the sampling interval was determined to be 40 min,and the in vitro recovery rate of the risedronate sodium probe was(45.85±0.63)%under this condition.When the flow rate and temperature of the perfusate remained constant,the in vitro recovery rates of the probe under different concentrations of risedronate sodium did not change significantly,and the in vitro recovery rates and loss rates of the probe were approximately equal(RSD=1.82%).Conclusion The established skin microdialysis method of risedronate sodium can be used for the study of the percutaneous absorption pharmacokinetics of risedronate sodium.