磷酸哌嗪宝塔糖含量测定方法的优化  

Optimization of the content determination method of trochisci piperazine phosphate

作　　者：杨梅 伍良涌[1] 李玮玲[1] 董顺玲[1] YANG Mei;WU Liangyong;LI Weiling;DONG Shunling(Guangzhou Institute for Drug Control,Guangzhou 510160,China)

机构地区：[1]广州市药品检验所,广州510160

出　　处：《中国药品标准》2023年第6期605-610,共6页Drug Standards of China

基　　金：国家药典委员会标准修订研究课题(课题编号:2018H103)。

摘　　要：目的:优化磷酸哌嗪宝塔糖的含量测定方法。方法:建立非水溶液测定法(电位滴定)和高效液相色谱法(外标法)分别对磷酸哌嗪宝塔糖进行含量测定。实验对非水溶液测定法和高效液相色谱法进行了相应的方法学验证。两种方法均与原方法(苦味酸沉淀法)比较,从而确定最优方法。结果:非水溶液测定法:样品经甲酸溶解,冰醋酸稀释后,照电位滴定法,用高氯酸滴定液(0.1 mol·L^(-1))滴定,并将滴定结果用空白试验校正,每1 mL高氯酸滴定液(0.1 mol·L^(-1))相当于10.11 mg的C_(4)H_(10)N_(2)·H_(3)PO_(4)·H_(2)O;高效液相色谱法:采用酰胺基键合硅胶(Waters XBridge?BEH Amide色谱柱4.6 mm×250 mm,5μm或效能相当的色谱柱)为填充剂,以0.05 mol·L^(-1)磷酸二氢钾溶液(用10%KOH溶液调pH至5.3)-乙腈(40∶60)为流动相,检测波长为210 nm,进样量10μL,该方法专属性高,重复性好,磷酸哌嗪峰形较好,结果准确。结论:经过多方面考量(HPLC暂无法定标准物质、非水溶液测定法无需对照品),建议非水溶液测定法(电位滴定)对磷酸哌嗪宝塔糖进行含量测定,与原方法相比,该方法操作简便、重复性好,辅料干扰在可接受范围内(1%),达到了磷酸哌嗪宝塔糖含量测定方法优化的目的。Objective:To optimize the content determination method of trochisci piperazine phosphate.Methods:Non-aqueous solution method(potentiometric titration) and high-performance liquid chromatography(HPLC,external standard method) were established for the content determination of trochisci piperazine phosphate and validated,and subsequently the optimal method was confirmed compared to the original method(picric acid precipitation method).Results:Non-aqueous solution method:samples were dissolved in formic acid,diluted with glacial acetic acid,and then titrated with perchloric acid titration solution(0.1 mol·L~(-1)).Every 1 mL of perchloric acid titration solution(0.1 mol·L~(-1)) was equivalent to 10.11 mg of C_4H_(10)N_2·H_3PO_4·H_2O;HPLC method parameters were as follows:Amide bonded silica gel(Waters XBridge?;Amide chromatographic column 250 mm×4.6 mm,5 μm or efficiency of chromatographic column) as a filler,0.05 mol·L~(-1) potassium dihydrogen phosphate solution(pH adjusted to 5.3 with 10% KOH solution) and acetonitrile(40∶60) as a mobile phase,detection wavelength of 210 nm,injection volume of 10 μL.The method had high specificity and reproducibility,and phosphate piperazine peak shape was good.Conclusion:Considering many factors(no legal standard substance for HPLC so far,while non-aqueous solution method not needed standard substance),non-aqueous solution method(potentiometric titration) was proposed for the optimization of the content determination of trochisci piperazine phosphate with simple operation,good repeatability and acceptable interference range(1%) of excipients.

关 键 词：磷酸哌嗪宝塔糖 含量测定 非水溶液测定法 高效液相色谱法 方法优化 

分 类 号：R921.2[医药卫生—药学]