超高效液相色谱-四极杆飞行时间质谱法测定大鼠血浆中的N6-羟苄腺苷  

Determination of N^6-(4-hydroxybenzyl)adenine riboside in rat plasma by ultra performance liquid chromatographyquadrupole time of flight mass spectrometry

作　　者：唐春兰[1,2] 王莉[1] 程孟春[1] 刘欣欣[1] 肖红斌[1] 

机构地区：[1]中国科学院大连化学物理研究所中国科学院分离分析化学重点实验室,辽宁大连116023 [2]中国科学院大学,北京100049

出　　处：《色谱》2015年第7期699-703,共5页Chinese Journal of Chromatography

基　　金：国家自然科学基金项目(81001629);重大新药创制专项课题(2014XZ09304-307)

摘　　要：建立了测定大鼠血浆中N6-羟苄腺苷的超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF-MS)分析方法,并应用于N6-羟苄腺苷药代动力学研究。采用Agilent ZORBAX SB-C18色谱柱(150 mm×3 mm,1.8μm)对目标物分离,以0.2%(v/v)甲酸水溶液和乙腈为流动相进行梯度洗脱;以6-苄氨基嘌呤作为内标,在电喷雾离子源正离子模式下进行定量分析。结果表明:N6-羟苄腺苷在0.625~160 ng/mL的范围内线性关系良好(r>0.99);方法的回收率在88.41%~108.26%之间;检出限达到0.1 ng/mL;日内和日间准确度(以RE计,RE=(测定浓度-加标浓度)/加标浓度×100%)均在±15%之内,精密度(以RSD计)均小于6%。该方法选择性好,灵敏度高,重现性好,结果准确,可用于N6-羟苄腺苷的血药浓度监测及药代动力学研究。An ultra performance liquid chromatography-quadrupole time of flight mass spec-trometry（ UPLC-QTOF-MS）method was developed and validated for the determination of N 6-（ 4-hydroxybenzyl ） adenine riboside and its pharmacokinetics in rat plasma. The chromato-graphic conditions were optimized. The separation was performed on an Agilent ZORBAX SB-C18 column（150 mm×3 mm,1. 8 μm）with a gradient elution of 0. 2%（v/v）formic acid aque-ous solution and acetonitrile as the mobile phases at a flow rate of 0. 35 mL/min. The detection was accomplished in positive mode with electrospray ionization（ ESI）by UPLC-QTOF-MS,and 6-benzylamino purine was used as the internal standard（ IS）. The results showed that the linear range of calibration curve was 0. 625-160 ng/mL for N6-（4-hydroxybenzyl）adenine riboside in rat plasma with the correlation coefficient more than 0. 99. The recoveries were 88. 41% -108. 26%. The limit of detection was 0. 1 ng/mL. The intra-day and inter-day precisions（ RSDs） were less than 6%,and intra-day and inter-day accuracies（ REs,RE=（ measured concentration-spiked concentration）/spiked concentration×100%）were less than ±15%. The method is rap-id,sensitive and accurate for the quantitation of N6-（4-hydroxybenzyl）adenine riboside,which can be used for the study of pharmacokinetics of N6-（4-hydroxybenzyl）adenine riboside.

关 键 词：超高效液相色谱-四极杆飞行时间质谱 N6-羟苄腺苷 药代动力学 大鼠血浆 

分 类 号：O658[理学—分析化学]