培哚普利叔丁胺中差向异构体分离测定方法研究  

Separation of perindopril tert-butylamine and(±)-1”epi-perindopril by high performance liquid chromatography

作　　者：周怡[1] 金薇 杨永健 ZHOU Yi;JIN Wei;YANG Yong-jian(Chinese Pharmacopoeia Commission,Beijing 100061,China;Shanghai Institute for Food and Drug Control,Shanghai 201203,China;National Medical Products Administration Key Laboratory for Quality Analysis of Chemical Drug Preparations,Shanghai 201203,China)

机构地区：[1]国家药典委员会,北京100061 [2]上海市食品药品检验研究院,上海201203 [3]国家药品监督管理局化学药品制剂质量分析重点实验室,上海201203

出　　处：《药物分析杂志》2024年第4期721-728,共8页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立一种快速液相色谱方法分离培哚普利叔丁胺及(±)-1”-差向-培哚普利叔丁胺(差向异构体),并对该差向异构体进行测定。方法:采用Agilent Poroshell CS-C18(100 mm×3.0 mm,2.7μm)色谱柱,以0.15%庚烷磺酸钠溶液(磷酸调节pH 2.0)-乙腈/戊醇(217∶3)(82∶18)为流动相,流速0.8 mL·min^(-1),柱温50℃,进样量2μL,在215 nm波长处分离培哚普利及(±)-1”-差向-培哚普利。结果:培哚普利及(±)-1”-差向-培哚普利在25 min内依次出峰,峰谷比和分离度满足测定要求。培哚普利叔丁胺及其差向异构体均在2~2000μg·mL^(-1)范围内线性关系良好(r>0.999),定量限(S/N约10)和检测限(S/N约3)均分别约为1.0μg·mL^(-1)和0.3μg·mL^(-1)。差向异构体低、中、高3个浓度的平均加样回收率为97.2%(RSD=1.8%,n=9)。10批样品中(±)-1”差向-培哚普利叔丁胺含量均在0.025%~0.078%。结论:建立的培哚普利叔丁胺中(±)-1”-差向-培哚普利叔丁胺的液相色谱测定方法,与现行药典收载色谱方法相比可极大缩短平衡与分离时间,提高分离效率和检测灵敏度,重现性好,可有效用于培哚普利叔丁胺的生产质量控制。Objective:To develop an HPLC method for the separation of perindopril tert-butylamine and its epi⁃mer[(±)-1”-epi-perindopril tert-butylamine]and the determination of the epimer.Methods:Perindopril and(±)-1”-epi-perindopril were separated on an Agilent Poroshell CS-C18 column(100 mm×3.0 mm,2.7μm)maintained at 50℃with the mobile phase containing a mixture of 0.15%sodium heptanesulfonate solution(adjusted to pH 2.0 with phosphoric acid)and acetonitrile-pentanol(217∶3)(82∶18,V/V)at 0.8 mL·min^(-1),and the detection wavelength was set at 215 nm.The injection volume was 2μL.Results:(±)-1”-epi-perindopril and perindopril were separated successfully in 25 min with peak to valley ratio more than 3.0 or a resolution factor of 1.7.Good linear relationships were established between the peak response and the concentration in the range of 2-2000μg·mL^(-1) for the epimer and perindopril tert-butyl⁃amine(r>0.999).The quantitative limits(S/N=10)were both about 1.0μg·mL^(-1),and the detection limits(S/N=3)were both 0.3μg·mL^(-1).The spiked recovery of the epimerer was 97.2%(RSD=1.8%,n=9).The content of(±)-1”-epi-perindopril tert-butylamine in 10 batches of samples ranged from 0.025%to 0.078%.Conclusion:The proposed method enhances the resolution efficiency,shows high accuracy,repeatabili⁃ty and stability.It can be effectively employed for the quality control of perindopril tert-butylamine.

关 键 词：培哚普利叔丁胺 (±)-1”差向-培哚普利叔丁胺 差向异构体 高效液相色谱 异构体分离 杂质测定 质量控制 

分 类 号：R917[医药卫生—药物分析学]