HPLC法测定复方美托拉宗片中美托拉宗和缬沙坦的相关物质  

Determination of related substances for metolazone and valsartan in compound metolazone tablets by HPLC

作　　者：胡小琴[1,2] 程晓慧 唐雪梅[2,4] 刘燕[2] 喻芳邻[2] 杨阳[2] 梅乐[2] 李明媛[2] 刘承[1,2] 马丝雨 梅兴国[2] 郭嘉[1] 李志平[2] 

机构地区：[1]武汉工程大学化工与制药学院,武汉430070 [2]军事医学科学院毒物药物研究所,北京100850 [3]北京京丰制药集团有限公司,北京100850 [4]云南中医学院,昆明650500

出　　处：《国际药学研究杂志》2017年第4期369-374,379,共7页Journal of International Pharmaceutical Research

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09301003-001-009)

摘　　要：目的建立复方美托拉宗片中美托拉宗和缬沙坦相关物质的HPLC测定方法。方法采用Agilent Eclipse SBC18色谱柱(4.6 mm×250 mm,5μm),以0.01 mol/L磷酸二氢钾溶液(pH=3.5)-乙腈为流动相,梯度洗脱,流速:1.0 ml/min,柱温:30℃,检测波长:237 nm,进样量:20μl。结果美托拉宗、缬沙坦及其相关物质之间分离度良好;美托拉宗在3~30μg/ml、缬沙坦在0.1~2.0μg/ml、缬沙坦杂质B在0.08~2.0μg/ml范围内峰面积与浓度线性关系良好;其平均回收率分别为102.97%、100.81%和100.44%;该法的重复性及中间精密度均符合要求;检测用溶液在室温条件下放置24 h稳定。结论该法专属性强、灵敏度高、准确可靠,可用于复方美托拉宗片中美托拉宗和缬沙坦相关物质测定。Objective To establish an HPLC method to determine the related substances of metolazone and valsartan in compound metolazone tablets. Methods An Agilent Eclipse SB-C18 column （4.6 mm× 250 mm, 5 μm） was used with 0.01 mol/L KH2PO4 buffer （pH=3.5）-acetonitrile as the mobile phase with gradient elution at a flow rate of 1.0 ml/min. The column temperature was 30℃ and the detection wavelength was 237 nm. Injection volume was 20 μl. Results Metolazone, valsartan and related substance B of valsartan were separated completely. The calibration curves were linear within the range of 3- 30μg/ml for metolazone, 0.1-2.0 μg/ml for valsartan and 0.08-2.0 μg/ml for related substane B of valsartan. The average recoveries were 102.97%, 100.81% and 100.44%, respectively. The repeatability and intermediate precision met with requirements. The test solution was stable within 24 h. Conclusion The method is specific, sensitive, accurate and reliable, thereby can be used for the determination of metolazone and valsartan related substances in compound metolazone tablets.

关 键 词：复方美托拉宗片 美托拉宗 缬沙坦 高效液相色谱法 

分 类 号：R927[医药卫生—药学] O657.72[理学—分析化学]