液相色谱-质谱法同时筛查并测定中成药中添加的9种抗病毒类化学药物  

Simultaneous Determination of Nine Antiviral Agents Illegally Adulterated into Traditional Chinese Medicines by HPLC-MS /MS

作　　者：黄晓君[1] 高青[1] 朱晓月[1] 张喆[1] 田洁[2] 

机构地区：[1]北京市药品检验所,北京100035 [2]国家食品药品监督管理局药品审评中心,北京100038

出　　处：《中国药学杂志》2014年第5期419-422,共4页Chinese Pharmaceutical Journal

基　　金：北京市科委"添加剂;辅料;残留溶剂鉴别和检测平台建设"资助项目(Z111100074211021)

摘　　要：目的建立液相色谱质谱方法检测中成药中可能添加的9种抗病毒类药物利己韦林、阿昔洛韦、喷昔洛韦、齐多夫定、奈韦拉平、拉米夫定、甲磺酸沙奎那韦、盐酸金刚炕胶和盐酸吗琳胁。方法采用液相色谱-质谱方法，SCX-CR1：4混合填料 色谱柱，流动相A为0.1%（V/V）甲酸溶液（用氨水调pH值至3.5） ，流动相B为乙赌，梯度程序洗脱：0-12min，A相为90%→48〈）奋; 12 - 15日lin，A相为48%→20% ;15 -19 min，A相为20〈）毛→15% ;19 - 20 min，A相90% ;流速为O.2 mL · min - 1 ; 进样量为5μL，应用正离子检测，扫描方式定性检测采用子离子扫描（Productmode） ，定量检测采用选择反应监测（SRM）0结 果9种待iYJIJ药物在0.01 -100μg·mL-1内线性良好，高、中、低3个浓度的加样回收率为80.6% -117.7% ，进样精密度RSD为1.1 % - 8.1 %，检出限为0.002-0.01μg· mL ^-1;推测了各化合物的质谱裂解途径。结论 方法专属性好、灵敏度高，可同时检测中成药中9种抗病毒类药物，适合复杂基质中抗病毒药物的确认和测定。OBJECTIVE To develop an HPLC-MS method for qualitative and quantitative analysis of nine antiviral agents illegally adulterated in traditional Chinese medicines. METHODS The samples were separated on a CAPCELL P AK CR 1： 4 column （2. 0 mm x 150 mm, 5 fLm） by gradient elution with O. 1 % formic acid solution （adjusted to pH 3. 5 with ammonium hydroxide） as the mobile phase A and acetonitrile as the mobile phase B. The gradient elution program was as follows rf -12 min（90%A→48%A） ,12 -15 mine 48% A→20% A） ,15 -19 min（20% A→15% A） ,19 -20 min（90% A）. The flow rate was 0. 2 mL · min^ -1 and the injection volume was 5 fLL. After being separated by HPLC, the test solution was analyzed by mass spectrometer operated in positive ion mode and in product mode and SRM mode. RESULTS The calibration curves of the nine antiviral agents showed good linearity and the correlation coefficients were more than 0. 998. The recoveries at 3 spiked levels were in the range of 80.6% - 117. 7%. The limits of quantification were in the range of 0. 1 - 1 μg · g ^- 1. The fragmentation pattern of the nine antiviral agents was summarized. CONCLUSION The method is sensitive, specific, accurate and applicable to detect the nine antiviral agents in traditional Chinese medicines.

关 键 词：抗病毒药物 液相色谱-质谱 利巴韦林 阿昔洛韦 喷昔洛韦 齐多夫定 奈韦拉平 拉米夫定 甲磺酸沙奎那韦 盐酸金 刚烷胺 盐酸吗啉胍 

分 类 号：R917[医药卫生—药物分析学]