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芳香伯胺是一类典型的有毒有害物质,常用于生产某些着色剂,可通过皮肤、胃肠道和呼吸道进人人体,导致机体细胞的功能和结构发生变化,严重者可引发人体输尿管癌、肾癌、膀胱癌等恶性疾病[1-2]. 最新国标GB 31604.52-2021《食品接触材料及制品中芳香族伯胺迁移量的测定》规定单个芳香伯胺的检测低限为1.0 μg·kg−1[2]. 作为直接与药品接触的药用铝箔类,其中使用的着色剂和聚合物涂层中,都存在芳香族伯胺残留风险[3]. 现阶段,测定芳香伯胺的方法有气相色谱法、气相色谱-串联质谱法、分光光度法、液相色谱法、液相色谱-串联质谱法[4-6]等,但这些方法仍然存在灵敏度低、准确度低、操作繁琐、检测时间长以及检测的组分较少等问题. 本文在中国食品药品检定研究院发布的药用复合膜、袋(含铝箔类)中29种芳香伯胺液相-质谱联用测定法基础上[7],建立了药用铝箔中34种芳香伯胺的UPLC-MS/MS测定方法,为有效控制药品包装材料,保障用药安全提供技术参考.
超高效液相色谱串联三重四极杆质谱法测定药用铝箔中34种芳香伯胺
Determination of 34 primary aromatic amines in medicinal aluminum foil by ultra performance liquid chromatography tandem triple quadrupole mass spectrometry
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摘要: 本文建立了超高效液相色谱串联三重四极杆质谱法(UPLC-MS/MS)检测药用铝箔类中34种芳香伯胺的含量. 采用Waters ACQUITY UPLC-HSS T3(100 mm×2.1 mm I.D.,1.8 μm)色谱柱,以0.1 %甲酸水溶液-乙腈为流动相,梯度洗脱,流速为0.4 mL·min−1,柱温为40 ℃. 采用电喷雾离子源(ESI+),工作模式为多反应监测模式(MRM). 34种芳香伯胺在1—100 ng·mL−1浓度范围内均具有较好的线性关系(r >0.999),各化合物保留时间和峰面积的相对标准偏差均小于0.21 %和5.00 %,加标回收率在73.5 %—114.8 %之间. 该方法具有灵敏度高、重复性好、准确度高的特点,可用于药用铝箔中34种芳香伯胺的测定.
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关键词:
- 芳香伯胺 /
- 药用铝箔 /
- UPLC-MS/MS.
Abstract: An ultra performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-MS/MS) method was developed for the determination of 34 primary aromatic amines in medicinal aluminum foils. Waters ACQUITY UPLC-HSS T3 (100 mm × 2.1 mm I.D., 1.8 μm) chromatographic column was used, with 0.1% formic acid aqueous solution-acetonitrile as mobile phase and gradient elution. The flow rate was 0.4 mL·min−1, column temperature was 40 °C. Electrospray ion source (ESI+) was used, and the working mode was multi-reaction monitoring mode (MRM). The 34 primary aromatic amines had satisfactory linear relationships in the concentration range of 1—100 ng·mL−1 (r>0.999). The relative standard deviations of retention time and peak area of each compound were less than 1.21% and 5.00%, respectively. The recoveries were between 73.5% and 114.8%. The established method has the characteristics of high sensitivity, good repeatability and high accuracy, and is feasible for the determination of 34 primary aromatic amines in medicinal aluminum foil.-
Key words:
- primary aromatic amines /
- medicinal aluminum foil /
- UPLC-MS/MS.
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表 1 34种芳伯胺的MRM参数
Table 1. MRM parameters of 34 primary aromatic amines
化合物 CAS 前体离子 产物离子 Q1 Pre/V CE/V Q3 Pre/V 对苯二胺 106-50-3 109.2 65.1*,92.1 -13,-14 -24,-20 -11,-18 间苯二胺 108-45-2 109.2 65.1*,92.1 -10,-13 -24,-19 -24,-16 2,4-二氨基甲苯 95-80-7 123.2 77.1*,106.1 -11,-10 -29,-19 -14,-11 4.4'-二氨基二苯醚 101-80-4 201.2 108.1*,80.0 -10,-15 -22,-35 -22,-15 2,6-二氨基甲苯 823-40-5 123.2 77.1*,106.1 -11,-11 -29,-22 -29,-20 联苯胺 92-87-5 185.2 167.1*,168.1 -14,-14 -27,-21 -17,-17 4,4'-二氨基二苯甲烷 101-77-9 199.2 106.0*,77.0 -15,-15 -25,-54 -10,-15 苯胺 63-53-3 94.0 77.1*,51.0 -19,-11 -23,-32 -14,-20 1,5-二氨基萘 2243-62-1 159.0 115.1*,143.1 -12,-13 -34,-24 -20,-27 对甲氧基苯胺 104-94-9 124.1 92.1*,109.1 -15,-26 -25,-22 -21,-19 邻甲氧基苯胺 90-04-0 124.1 109.1*,92.1 -26,-15 -22,-25 -19,-21 邻甲苯胺 95-53-4 108.2 91.1*,65.1 -10,-10 -22,-28 -17,-24 3,3'-二甲氧基联苯胺 119-90-4 245.2 230.1*,213.2 -11,-10 -19,-20 -24,-14 3,3'-二甲基联苯胺 119-93-7 213.2 80.1*,196.1 -17,-18 -35,-20 -19,-20 2,4-二氨基苯甲醚 615-05-4 139.1 124.1*,108.1 -11,-11 -17,-19 -12,-20 3-氨基对甲苯甲醚 120-71-8 138.2 123.1*,77.1 -12,-12 -21,-35 -22,-28 2,6-二甲基苯胺 87-62-7 122.2 77.05*,107.1 -10,-10 -28,-22 -14,-21 3,3'-二甲基-4,4'-二氨基二苯甲烷 838-88-0 227.2 120.1*,178.1 -19,-11 -25,-27 -12,-18 2,4'-二氨基二苯甲烷 1208-52-2 199.2 106.0*,77.0 -15,-15 -25,-54 -10,-15 对氯苯胺 106-47-8 128.1 93.1*,111.1 -11,-10 -22,-17 -16,-16 2,4-二甲基苯胺 95-68-1 122.2 77.1*,107.1 -10,-10 -31,-22 -14,-21 2,4,5-三甲基苯胺 137-17-7 136.2 91.1*,121.15 -11,-11 -24,-21 -17,-26 4,4'-二氨基二苯硫醚 139-65-1 217.1 124.05*,0.05 -17,-18 -23,-48 -24,-29 2-萘胺 91-59-8 143.8 127.1*,117.1 -12,-13 -26,-22 -24,-12 2,4,6-三甲基苯胺 88-05-1 136.2 91.1*,121.15 -11,-11 -24,-21 -17,-26 1-萘胺 134-32-7 143.8 127.1*,117.1 -12,-13 -26,-22 -24,-12 2,2'-二氨基二苯甲烷 6582-52-1 199.2 106.0*,77.0 -15,-15 -25,-54 -10,-15 4-氯邻甲苯胺 95-69-2 142.1 107.1*,125.0 -12,-11 -20,-25 -20,-22 2-氨基-4-硝基甲苯 99-55-8 153.1 107.0*,90.2 -13,-11 -17,-21 -19,-18 4-氨基联苯 92-67-1 170.1 152.1*,153.1 -12. -12 -30,-30 -22,-22 3,3'-二氯联苯胺 91-94-1 253.1 217.1*,182.1 -12,-12 -22,-28 -23,-18 对氨基偶氮苯 60-09-3 198.0 77.1*,93.2 -15,-15 -23,-23 -14,-20 4,4'-次甲基-双-(2-氯苯胺) 101-14-4 267.1 140.0*,95.05 18,12 -25,-32 -23,-13 邻氨基偶氮甲苯 97-56-3 226.2 91.1*,121.1 -11,-11 -23,-23 -17,-20 *表示定量离子 表 2 方法学考察结果
Table 2. Methodological investigation results
化合物 相关系数 信噪比 检出限/(ng·mL−1) 定量限/(ng·mL−1) 回收率±RSD/% 对苯二胺 0.9998 12 0.29 0.86 91.1±0.13 间苯二胺 0.9999 32 0.29 0.87 92.6±0.86 2,4-二氨基甲苯 0.9997 20 0.15 0.46 102.3±4.18 4,4-二氨基二甲醚 0.9997 11 1.46 4.41 88.0±0.57 2,6-二氨基甲苯 0.9999 22 0.16 0.49 74.2±2.22 联苯胺 0.9998 61 0.05 0.16 82.4±4.09 4,4-二氨基二苯甲烷 0.9998 43 0.08 0.24 76.8±1.00 苯胺 0.9999 31 0.22 0.66 100.7±3.71 1,5-萘二胺 0.9999 22 0.10 0.29 93.7±3.54 对甲氧基苯胺 0.9998 125 0.03 0.08 87.6±0.26 邻甲氧基苯胺 0.9997 196 0.02 0.06 95.1±1.20 邻甲苯胺 0.9994 132 0.03 0.08 112.7±0.35 3,3-二甲氧基联苯胺 0.9996 80 0.03 0.10 106.4±3.77 3,3-二甲基联苯胺 0.9995 177 0.02 0.05 100.7±1.54 2,4二氨基苯甲醚 0.9998 53 0.06 0.17 112.4±1.37 3-氨基对甲苯甲醚 0.9996 111 0.03 0.09 106±0.87 2,6-二甲基苯胺 0.9995 48 0.06 0.19 111.3±0.97 3,3-二甲基-4,4-二氨基二苯甲烷 0.9996 79 0.10 0.03 114.5±0.39 2,4-二氨基二苯甲烷 0.9993 107 0.03 0.09 103.6±3.13 对氯苯胺 0.9996 100 0.03 0.10 108.3±2.53 2,4-二甲基苯胺 0.9993 14 0.23 0.70 106.5±2.34 2,4,5-三甲基苯胺 0.9996 30 0.12 0.35 102.7±0.93 4,4-二氨基二苯硫醚 0.9996 105 0.01 0.03 112.3±1.01 b-萘胺 0.9998 141 0.01 0.03 114.5±1.06 2,4,6-三甲基苯胺 0.9998 141 0.03 0.08 107.8±0.69 a-萘胺 0.9996 225 0.01 0.02 114.2±0.61 2,2-二氨基二苯甲烷 0.9998 107 0.03 0.10 107.4±1.66 4-氯邻甲苯胺 0.9995 111 0.01 0.03 107.4±0.21 2-氨基-4-硝基甲苯 0.9996 16 1.10 3.31 108.4±2.20 4-氨基联苯 0.9998 149 0.02 0.07 112.6±1.68 3,3-二氯联苯胺 0.9994 37 0.07 0.21 108±0.12 对氨基偶氮苯 0.9998 133 0.03 0.08 101.5±1.42 4,4-次甲基-双-(2-氯苯胺) 0.9995 42 0.09 0.26 109.4±0.51 邻氨基偶氮甲苯 0.9996 71 0.05 0.15 109.7±0.89 -
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