UPLC-QTOF/MS法分析盐酸奈必洛尔中痕量遗传毒性杂质A和B  

Trace determination of genotoxic impurities A and B in nebivolol hydrochloride by UPLC-QTOF/MS

作　　者：陈菁菁 杨小玲 李琴[2] 

机构地区：[1]杭州容立医药科技有限公司,杭州310023 [2]浙江省医学科学院,杭州310013

出　　处：《药物分析杂志》2016年第11期2035-2040,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：浙江省中医药科技计划(2016ZQ011)

摘　　要：目的:建立超高效液相色谱-四极杆飞行时间串联质谱法(UPLC-QTOF/MS)定量检测盐酸奈必洛尔(NBLR)原料中遗传毒性杂质A(A1:6-氟-2-[1-羟基-2-(4-甲苯磺酰氧基)-(1S)-乙基]-(2R)-3H,4H-苯并吡喃和A2:6-氟-2-[1-羟基-2-(4-甲苯磺酰氧基)-(1R)-乙基]-(2S)-3H,4H-苯并吡喃)和B(B1:6-氟-2-[1-羟基-2-(4-甲苯磺酰氧基)-(1S)-乙基]-(2S)-3H,4H-苯并吡喃和B2:6-氟-2-[1-羟基-2-(4-甲苯磺酰氧基)-(1R)-乙基]-(2R)-3H,4H-苯并吡喃)。方法:采用色谱柱Acquity UPLC~? BEH C_(18)(2.1 mm×50 mm,1.7μm),以甲醇-0.2%氨水(醋酸调pH 7.2)(60∶40)为流动相,流速0.4 mL·min^(-1),柱温35℃,进样量5μL;ESI正离子灵敏度模式下选择m/z 389.08[M+Na]^+对杂质A和B同时进行检测,毛细管电压3.5 kV,离子源温度100℃,气化温度350℃。结果:杂质A和B质量浓度在1.5~18 ng·mL^(-1)范围内线性关系良好,相关系数分别为0.998 0和0.996 7,定量下限均为1.5 ng·mL^(-1),杂质A和B平均回收率(n=9)分别为99.7%和100.0%,样品中杂质A和B测定的重复性良好(n=6),RSD分别为6.2%和4.7%;对原料进行检查,均未检出杂质A和B。结论:经方法学验证,本方法可同时检测NBLR原料中的遗传毒性杂质A和B。Objective： To determine impurities A （ A 1 ： 6-fluoro-2- [ 1-hydroxy-2- （ 4-toluenesulfonyloxy ） - （ 1S ） -ethyl ] - （ 2R ） -3H, 4H-benzopyran and A2： 6-fluoro-2- [ 1-hydroxy-2- （ 4-toluenesutfonyloxy ） - （ 1R ） -ethyl ] - （ 2S ） -3H, 4H-benzopyran ） and B （ B1 ： 6-fluoro-2- [ 1-hydroxy-2- （ 4-toluenesulfonyloxy ） - （ 1S ） -ethyl ] - （ 2S ） -3H, 4H-benzopyran and B2： 6-fluoro-2- [1-hydroxy-2- （ 4-toluenesulfonyloxy ） - （ 1R ） -ethyl ] - （ 2R ） -3H, 4H-benzopyran ） in nebivolol hydrochloride （ NBLR ） by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, （UPLC-QTOF/MS）. Methods： The separationwas carried out on an Acquity UPLC1 BEH C18 （2. 1 mm × 50 mm, 1.7 μm ）column with the mobile phase consisting of methanol-0. 2% ammonia （ acetic acid adjust pH to7.2 ） （ 60 ： 40 ）. The flow rate was 0. 4 mL. min-1, the column temperature was 35℃, and the injection volume was 5 μL. The results of quadrupole time-of-flight mass spectrometer was equipped with ESI （ in the positive mode ） and detected at m/z 389.08 [ M＋Na ]＋ for both A and B. The source parameters were as follows, electrospray capillary voltage of 3.5 kV, source temperature of 100 ℃ and desolvation temperature of 350 ℃. Results： The calibration curves of impurities A and B were in a good linearity within concentration range of 1.5-18 ng. mL-1, and the correlation coefficients were 0. 998 0 and 0. 996 7, respectively. The limits of quantification of impurities A and B were 1.5 ng. mL-1, the recoveries of impurities A and B were 99.7% and 100.0%, respectively. Repetitions of impurities A and B in sample were fine, with RSD （ n=6 ） of 6. 2% and 4.7%, respectively. The impurities A and B in nebivolol hydrochloride were not detected. Conclusion： The methodology validation proved that this UPLC-QTOF/MS method is useful as a quality control method for simultaneous trace analysis of impurities A and B in nebivolol hydro

关 键 词：盐酸奈必洛尔(NBLR) 遗传毒性杂质 磺酸酯 苯并吡喃 Β受体阻滞剂 超高效液相质谱 

分 类 号：R917[医药卫生—药物分析学]