直接进样-气质联用法测定头孢曲松钠中10种残留溶剂及其质量评价研究

Determination of 10 residual solvents in ceftriaxone sodium and quality evaluation by direct injection gas chromatography-tandem mass spectrometry

目的建立直接进样测定头孢曲松钠中10种残留溶剂的气质联用方法,对不同企业的样品进行质量评价研究。方法采用Agilent J&W DB-624UI色谱柱(60 m×0.250 mm,1.4μm);进样口温度为235℃,初始温度30℃,保持12 min,以5℃·min^(-1)速率升至100℃,保持l min,再以50℃·min^(-1)速率升至235℃,保持10 min;流速3 mL·min^(-1);不分流进样;进样体积0.2μL;在选择性离子检测模式下,以正丁醇为溶剂直接进样检测,外标法定量。采用Plackett-Burman试验设计结合Pareto图对方法耐用性影响因素进行考察,并对51家企业的51批样品的残留溶剂进行考察。结果10种残留溶剂分别在各自浓度范围内与峰面积线性关系良好(r均大于0.999);回收率为99.7%~103.9%,RSD均小于2%;检测限范围为0.006~67.750μg·g-1;方法耐用性良好。51批样品中丙酮均有检出,甲醇、乙腈及异丙醇3种残留溶剂部分企业有检出。结论该方法操作简便、准确可靠、样品用量少,试剂来源广、易得,适用于头孢曲松钠残留溶剂的含量测定及质量控制。

Objective To establish a direct injection gas chromatography-tandem mass spectrometry(GCMS/MS)method to determine 10 residual solvents in ceftriaxone sodium and evaluate its quality.Methods An Agilent J&W DB-624UI capillary column(60 m×0.250 mm,1.4μm)was used.The temperature of injection was 235℃,the initial column temperature was 30℃,held for 12 min and then increased at a rate of 5℃·min^(-1)to 100℃,held for 1 min,and finally increased at a rate of 50℃·min^(-1)to 235℃,held for 10 min.The flow rate was 3 mL·min^(-1).Splitless injection was adopted,and the injection volume was 0.2μL.The mass spectrometer was operated with the mass scanning combining selective ion monitoring,n-butanol was used for direct-injection detection,and external standard method was used for quantification.Plackett-Burman design combined with Pareto chart was used to determine the factors influencing the robustness of the method.The method was used to measure residual solvents in 51 batches from 51 producers.Results The 10 residual solvents had good linear relationship within their respective concentration ranges(r>0.999);the recoveries ranged 99.7%~103.9%,with RSD less than 2%;the detection limits ranged 0.006~67.750μg·g-1.Acetone was detected in 51 batches of samples while methanol,acetonitrile and isopropanol were partially detected.Conclusion The method is simple,accurate and reliable,with few samples needed,and easy availability of reagents.It can be used for the determination and quality evaluation of residual solvents in ceftriaxone sodium.