目的 建立一种快速、准确检测降压类中成药及调节血压类保健食品中非法添加34种化学药的方法。方法 采用UPLC-MS/MS法,以Waters Acquity BEH-C₁₈柱(100 mm×2.1 mm,1.7 μm)为色谱柱,以0.1%甲酸甲醇溶液(A)-0.1%甲酸水溶液(B)为流动相,梯度洗脱(0～5 min,32% A;5～8 min,32%～50% A;8～12 min,50% A;12～14 min,50%～60% A;14～16 min,60%～80% A;16～18 min,80% A;18～19 min,80%～90% A;19～20 min,90%～100% A;20～21 min,100% A;21～22 min,100%～32% A);体积流量0.2 mL/min,柱温40 ℃。选择ESI离子源、正离子扫描、多反应监测(MRM)模式测定34种临床常用的化学降压药,通过比较MRM通道中样品峰与对照品峰的分子离子峰、二级碎片离子峰、色谱保留时间等信息确定添加的化学药物,并根据外标法以质谱峰面积计算添加药物的准确量。结果 在上述色谱及质谱条件下,34种化学药物可乐定、卡托普利、利血平、甲基多巴、氢氯噻嗪、呋塞米、吲达帕胺、米诺地尔、肼屈嗪、阿替洛尔、赖诺普利、地巴唑、美托洛尔、比索洛尔、哌唑嗪、特拉唑嗪、普萘洛尔、依那普利、喹那普利、贝那普利、地尔硫卓、多沙唑嗪、尼卡地平、硝苯地平、氨氯地平、尼莫地平、非洛地平、尼群地平、尼索地平、缬沙坦、替米沙坦、坎地沙坦酯、厄贝沙坦、奥美沙坦酯的分离度良好,方法检测限(LOD)均在0.1～0.5 ng/g,定量限(LOQ)均在0.3～1.5 ng/g,标准加样回收率均在81.4%～118.9%。结论 本法简便、准确,灵敏度高,可作为降压类中成药及调节血压类保健食品中非法添加化学降压药的定量测定方法。

Objective To establish a rapid and accurate method for the determination of 34 chemical hypotensors which were illegally added into the blood pressure lowering class Chinese patent medicines (CPM) and the blood pressure regulating class health foods. Methods The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH-C₁₈ (100 mm × 2.1 mm, 1.7 μm) column with 0.1% formic acid methanol (A) and 0.1% formic acid water solution (B) as the mobile phase by gradient elution (0—5 min, 32% A; 5—8 min, 32%—50% A; 8—12 min, 50% A; 12—14 min, 50%—60% A; 14—16 min, 60%—80% A; 16—18 min, 80% A; 18—19 min, 80%—90% A; 19—20min, 90%—100% A; 20—21 min, 100% A; and 21—22 min, 100%—32% A) at a flow rate of 0.2 mL/min, and the column temperature was 40 ℃. A positive-ion (ESI⁺) source and a MRM mode were used to separate and quantitatively determine the chemical hypotensors. The obtained molecularions, fragment ions, and retention time for MRM channels were used to identify the 34 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate content of chemical hypotensors in the blood pressure lowering class CPM and the blood pressure regulating class health foods. Results A good resolution of 34 kinds of chemical drugs, including clonidine, captopril, yohimban-16-carboxylicacid, L-tyrosine, hydrochlorothiazide, furosemide, indapamide, minoxidil, hydralazine, atenolol, lisinopril, dibazole, metoprolol, bisoprolol, prazosin, terazosin, propranolol, enalapril, quinapril, benazepril, dilthiazem, doxazosin, nicardipine, nifedipine, amlodipine, nimodipine, felodipine, nitrendipine nisoldipine, valsartan, telmisartan, candesartan cilexetil, rbesartan, and olmesartan medoxomil was obtained under this UPLC and MS/MS condition. The limits of qualitative and quantitative were in the range of 0.1—0.5 and 0.3—1.5 ng/g. The standard addition recoveries were in the range of 81.4%—118.9%. Conclusion The method is simple, accurate, and with high sensitivity, which can be used for the determination of illegally added chemical hypotensors in CPM and health foods.

浙江省公益性技术应用研究计划资助项目(2013C37103);"十二五"浙江省高校重点学科(药理学)项目资助