梯度洗脱RP-HPLC法测定琥珀酸去甲文拉法辛中有关物质

目的:建立RP-HPLC法测定琥珀酸去甲文拉法辛中有关物质;主要包括:4-(2-二甲氨基乙基)苯酚(杂质A),1-[2-氨基-1-(4-苯酚)乙基]环己醇(杂质B),4-[1-(1-环己醇)-2-(甲氨基)乙基]苯酚(杂质C),2-(1-环己醇)-2-(4-苯酚)-N,N-二甲基-N-氧化乙胺(杂质D),4-[2-二甲氨基-1-(1-环己醇)乙基]-2-(｛5-[2-二甲氨基-1-(1-环己醇)乙基]-2-羟基苯基｝甲基)苯酚(杂质E),2-(1-环己烯)-2-(4-苯酚)-N,N-二甲基乙胺(杂质F),1-[2-二甲氨基-1-(4-甲氧基苯基)乙基]环己醇(杂质G),2-环己基-2-(4-苯酚)-N,N-二甲基乙胺(杂质H)。方法:采用色谱柱Waters Symmetry C₁₈(250 mm×4.6 mm,5 μm),以0.05 mol·L^-1 磷酸二氢铵缓冲液(pH 4.0)-乙腈为流动相,梯度洗脱,流速1.0 mL·min^-1,柱温30 ℃,检测波长225 nm。结果:琥珀酸去甲文拉法辛及其8个已知杂质质量浓度在各自线性范围内与峰面积的线性关系良好(r²≥0.999 0);琥珀酸去甲文拉法辛、杂质A、杂质B、杂质C、杂质D、杂质E、杂质F、杂质G和杂质H的检测限(S/N=3)分别为0.60、0.39、0.61、0.58、0.59、0.40、0.61、0.60和0.61 ng;各有关物质测定结果,杂质C为0.04%~0.05%,杂质E均为0.06%,杂质A、B、D、F、G和H均未检出,总杂质为0.10%~0.11%。结论:本方法可用于琥珀酸去甲文拉法辛的有关物质 测定。

Objective:To establish a RP-HPLC method for determination of the related substances in des-venlafaxine succinate.The impurities mainly included 4-(2-dimethylaminoethyl)phenol(impurity A), 4-[2-amino-1-(1-hydroxycyclohexyl)ethyl] phenol(impurity B),4-[1-(1-hydroxycyclohexyl)-2-(methylamino)ethyl] phenol(impurity C),2-(1-hydroxycyclohexyl)-2-(4-hydroxyphenyl)-N,N-dimethylethanamine oxide(impurity D),4-[2-(dimethylamino)-1-(1-hydroxycyclohexy)ethyl]-2-(｛5-[2-(dimethylamino)-1-(1-hydroxycyclohexy)ethyl]-2-hydroxyphenyl｝methyl)phenol(impurity E),4-(1-cyclohexenyl-2-(dimethylamino)ethyl)phenol(impurity F),1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol(impurity G),4-(1-cyclohexyl-2-(dimethylamino)ethyl)phenol(impurity H).Methods:The determination was performed on a Waters Symmetry C₁₈ column(250 mm×4.6 mm,5 μm)with the mobile phase consisting of a mixture of 0.05 mol·L^-1 phosphate buffer(pH 4.0)and acetonitrile by gradient elution at a flow rate of 1.0 mL·min^-1.The column temperature was 30 ℃,and the detective wavelength was 225 nm.Results:A good linearity was obtained in the measured concentration ranges for desvenlafaxine succi-nate and 8 impurities(r²≥0.999 0),and the detection limits(S/N=3)were 0.60,0.39,0.60,0.58,0.59,0.40,0.61,0.60 and 0.61 ng for desvenlafaxine succinate,impurity A,impurity B,impurity C,impurity D,impurity E,impurity F,impurity G and impurity H;The content of impurity C was 0.04%-0.05%,the content of impurity E was 0.06%,impurity A,impurity B,impurity D,impurity F,impurity G and impurity H were not detected,and the content of total impurities was 0.10%-0.11%.Conclusion:The established method can be used for determination of the related substances in desvenlafaxine succinate.