目的建立一种超高效液相色谱-四极杆串联线性离子阱质谱技术测定乳制品中8种青霉素类抗生素(青霉素G、氨苄西林、青霉素V、阿莫西林、苯唑西林、萘夫西林、氯唑西林、双氯西林)及其相应的代谢产物青霉噻唑酸(青霉素G噻唑酸、氨苄青霉噻唑酸、青霉素V噻唑酸、羟氨苄青霉噻唑酸、苯唑青霉噻唑酸、乙氧萘青霉噻唑酸、氯唑青霉噻唑酸、双氯青霉噻唑酸)残留的方法,并对市售乳制品中青霉素及青霉噻唑酸残留情况进行调查。方法乳制品样品中青霉素及青霉噻唑酸采用纯水超声提取,经乙腈沉淀蛋白,正己烷液液萃取除去脂肪,用氮气吹至近干,用乙腈-水(10∶90,V/V)复溶后,经0.22μm微孔滤膜过滤,经超高效液相色谱C_(18)柱(50 mm×2.1 mm,1.8μm)分离,选用乙腈-水(含0.1%甲酸)为流动相,梯度洗脱分离8种青霉素及相应青霉噻唑酸共16种组分;在优化的四极杆串联线性离子阱质谱条件下,采用ESI源、正离子模式、多反应监测方式,外标法定量,采用信息依赖采集扫描功能(IDA)结合增强子离子扫描(EPI)模式对检出阳性结果进行定性分析。结果方法的线性范围为1.0~200μg/L,8种青霉素及相应青霉噻唑酸在各种乳制品基质中均有良好的线性相关性,相关系数r在0.999 1~0.999 9之间,方法最低检测限为0.01~0.05μg/kg(固体乳粉)和0.002~0.010μg/kg(液体奶);方法回收率在80.0%~110.0%,相对标准差为0.16%~7.06%。结论该方法测定8种青霉素药物及相应代谢产物青霉噻唑酸的残留量简便、快速、定性准确,可以满足对青霉素类药物及其代谢产物残留的检测要求。 OBJECTIVE To establish a method for determination of 8 penicillin antibiotics (penicillin G, ampicillin, penicillin V, amoxicillin, oxacillin, nafcillin, Cloxacillin, dicloxacillin) and its corresponding metabolite penicilliothiazole (penicillin G thiazole, ampicillin thiazole, penicillin V thiazole, amoxicillin thiazole, oxacillin thiazole acid, B Penicillin, penicillin, dicloxacillin thiazole, and residues of penicillin and penicillin in commercially available dairy products were investigated. Methods Penicillin and penicillin in dairy products were extracted with pure water by ultrasonic wave. The protein was precipitated by acetonitrile and extracted by liquid-liquid extraction with n-hexane. The solution was blown to near dryness with nitrogen gas. The mixture was washed with acetonitrile-water (10:90, V / After being filtered, the solution was filtered through a 0.22 μm microporous membrane and separated on a C 18 column (50 mm × 2.1 mm, 1.8 μm) by ultra performance liquid chromatography. The mobile phase consisted of acetonitrile-water (containing 0.1% formic acid) Elution and separation of eight kinds of penicillins and corresponding penicillin thiazole 16 components; under the optimized quadrupole linear tandem mass spectrometry conditions, using ESI source, positive ion mode, multiple reaction monitoring, external standard method, Qualitative analysis of positive results was performed using the Information-Dependent Acquisition Scanning (IDA) combined with enhanced ion scan (EPI) mode. Results The linear range of the method was 1.0 ~ 200μg / L. There was a good linear correlation between the eight penicillins and the corresponding penicillin in all kinds of dairy products. The correlation coefficient was between 0.999 1 and 0.999 9, and the method was the lowest The detection limits were 0.01-0.05 μg / kg (solid milk powder) and 0.002-0.010 μg / kg (liquid milk). The recoveries were in the range of 80.0% -110.0% with relative standard deviations of 0.16-7.06%. Conclusion The method for the determination of penicillin drugs and the corresponding metabolites of penicillin thiazole acid residues simple, rapid, qualitative and accurate, to meet the penicillins drugs and their metabolites residues detection requirements.