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, 2.7 μm)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2 μL,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2~2 000 μg·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1.0 μg·mL-1和0.3 μg·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 epimer [(±)-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, 2.7 μm) 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 2 μL. 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 2-2 000 μg·mL-1 for the epimer and perindopril tert-butylamine(r> 0.999). The quantitative limits(S/N= 10) were both about 1.0 μg·mL-1,and the detection limits(S/N=3) were both 0.3 μg·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,repeatability and stability. It can be effectively employed for the quality control of perindopril tert-butylamine.
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