HPLC法检测抗青光眼新药(S)-OTS·HCl水溶液的稳定性  

Stability evaluation of antiglaucoma new drug(S)-OTS·HCl in solution by HPLC

作　　者：余年喜[1] 谢一凡[1] 杨丽敏[1] 陆阳[1] 

机构地区：[1]上海交通大学医学院药学系,上海200025

出　　处：《上海交通大学学报（医学版）》2010年第7期793-796,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委基金(06DZ19001)~~

摘　　要：目的建立测定(S)-OTS及其水解物6β-羟基-3α-对甲苯磺酰氧基莨菪烷(HTT)和对甲苯磺酸(TsOH)含量的高效液相色谱(HPLC)法,考察抗青光眼新药(S)-OTS·HCl水溶液的稳定性。方法 HPLC色谱条件:Diamonsil-C18为色谱柱;甲醇-10mmol/L磷酸二氢钠缓冲液(含5mmol/L四丁基溴化铵)(53:47)为流动相;流速1.0mL/min,紫外检测波长227nm,柱温31℃,进样量10μL。对建立的HPLC法进行相关验证试验。以0.03%(药用浓度)的(S)-OTS·HCl水溶液作为供试样品,利用已建立的HPLC法检测其溶质含量以考察稳定性。结果专属性试验显示,(S)-OTS与HTT和TsOH的色谱峰分离良好。线性关系试验表明,在系列对照品标准浓度范围内[(S)-OTS·HCl6.066～606.600μg/mL,HTT5.304～530.400μg/mL,TsOH3.034～303.400μg/mL],对照品(S)-OTS·HCl、HTT和TsOH与相应色谱峰面积呈线性相关(r2>0.999);灵敏度(检测限和定量限)、精密度、稳定性和方法回收率试验均符合要求。供试样品在室温下水解速度较快,其主成分(S)-OTS含量下降与水解物TsOH含量上升相吻合。结论建立了对主成分(S)-OTS及其水解物HTT和TsOH进行定量分析的HPLC法。药用浓度的(S)-OTS·HCl水溶液的稳定性受环境温度的影响,其水解易发生在磺酸酯部位。Objective To develop the method of high performance liquid chromatography （HPLC） for detection of contents of （S）-OTS and its hydrolysis products （1R,3S,5R,6S）-6-hydroxy-3-paramethylphenylsulfonyloxy tropane （HTT） and paratoluenesulfonic acid （TsOH）, and evaluate the stability of antiglaucoma new drug （S）-OTS·HCl in solution. Methods Chromatographic conditions for HPLC： chromatographic column, Diamonsil-C18; mobile phase, methanol-10 mmol/L sodium dihydrogen phosphate （containing 5 mmol/L tetrabutylammonium bromide） （53∶47）; flow rate, 1.0 mL/min; detection wavelength of violet, 227 nm; column oven temperature, 31 ℃; sample volume, 10 μL. Verification of the established HPLC method was performed. With 0.03% （S）-OTS·HCl in solution as samples, the established HPLC method was employed to detect the content of solute for stability evaluation. Results Specific tests indicated that HTT and TsOH were well resolved from each other and from （S）-OTS. Linear correlation test demonstrated that （S）-OTS, HTT and TsOH had linear correlation with chromatographic peak areas in the scope of standard concentration of serial controls [（S）-OTS·HCl 6.066-606.600 μg/mL,HTT 5.304-530.400 μg/mL,TsOH 3.034-303.400 μg/mL] （r2〉0.999）. The method conditions were fully validated with acceptable sensitivity （limit of detection and limit of quantitation）, precision, stability and recovery rate. The tested samples hydrolyzed rapidly under room temperature, and the decrease of content of its main component （S）-OTS was in line with the increase of content of its hydrolysis product TsOH. Conclusion The method of HPLC for quantitative analysis of main component （S）-OTS and its hydrolysis products HTT and TsOH is established. The stability of （S）-OTS·HCl in solution for medical purpose is influenced by temperature, and its hydrolysis usually takes place in sulfonate site.

关 键 词：(S)-OTS·HCl 水解物 稳定性 高效液相色谱法 

分 类 号：R927.2[医药卫生—药学]