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作为预防和治疗细菌与真菌性疾病应用最广泛的药物之一[1-2], 抗生素在我国生产和使用量巨大且滥用现象严重。多数抗生素难以被人和动物完全吸收代谢,约60%—80%以原形或代谢产物的形式排除体外进入环境水体,从而潜在影响饮用水源地水质安全[3-5]。近年来,水环境中的喹诺酮类、四环素类、磺胺类和大环内酯类等4类抗生素被频繁检出[6-8]。因此,建立快速同时测定饮用水源水中多种抗生素残留的方法对保障供水安全具有重要意义。
目前,国内外针对抗生素的主要检测方法有酶联免疫法[9-10]、高效液相色谱法[11-12]和高效液相色谱串联质谱法 [13-14]等。但酶联免疫法的特异性不够高,无法准确定量且存在假阳性的可能;高效液相色谱法存在检测抗生素种类有限、检出限高,容易受到复杂基质的干扰等缺点。而固相萃取-高效液相色谱串联质谱法(SPE-HPLC-MS/MS)因其灵敏度高、分析速度快、选择性强的优点,已成为环境中抗生素检测的首选分析方法[15-18]。然而,由于抗生素的种类繁多、化学结构复杂、性质差异较大,不同种类抗生素的前处理方法的差异化,方法合并后回收结果参差不齐[19],测定方法虽可以满足地表水中抗生素残留的分析需求[20],但难以达到饮用水源中超痕量残留浓度的检出要求。因此,为了满足不同种类抗生素的灵敏、快速检测的需要,亟需建立一种适用于多种抗生素同时测定的痕量检测方法。
本文通过优化固相萃取前处理条件、液相色谱和质谱参数等条件,考察方法的线性回归方程、相关系数、方法的检出限和回收率等指标,建立了一种目标污染物的固相萃取-高效液相色谱串联质谱的测定方法。最后,应用该方法对厦门市饮用水源地源水中4类13种抗生素残留情况进行了初步分析,为饮用水源地源水中抗生素残留研究提供了分析方法支撑。
测定13种抗生素的固相萃取-高效液相色谱串联质谱法优化与应用
Optimization and application of solid phase extraction-high performance liquid chromatography-tandem mass spectrometry for determination of 13 antibiotics
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摘要: 大量用于预防和治疗细菌和真菌性等疾病的抗生素药物未经完全代谢后最终进入自然水体,对饮用水源水质安全构成潜在威胁。为快速测定饮用水源水体中的抗生素残留,保障饮水安全,本论文建立一种固相萃取-高效液相色谱串联质谱法测定13种抗生素的分析方法。采用OASIS® HLB小柱对水样进行固相萃取富集和净化,以甲醇和0.5%的甲酸(含5 mmol·L−1乙酸铵)水溶液为流动相,经Kinetex®C18 色谱柱分离后采用三重四极杆串联质谱多反应监测模式分析。该方法检出限为0.05—1.66 ng·L−1,定量限为0.17—5.52 ng·L−1,回收率为70.2%—121.5%,相对标准偏差为1.1%—13.5%。该方法准确度高,灵敏度高,适用于饮用水源源水中痕量抗生素残留的测定。方法成功应用于厦门市饮用水源源水中抗生素残留分析,共检出7种抗生素,浓度范围为ND—32.6 ng·L−1。
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关键词:
- 高效液相色谱串联质谱法 /
- 抗生素 /
- 固相萃取 /
- 饮用水源
Abstract: Antibiotics are used for the prevention and treatment of bacterial and fungal diseases. The residual antibiotics end up in natural water bodies, leading to safe drinking water quality. In order to rapid determination antibiotic residues in drinking water and ensure the safety of drinking water, an analytical method was developed for the simultaneous determination of 13 antibiotics residues in 4 classes in waters of drinking water source by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. The samples were concentrated and purified with OASIS® HLB cartridge. Gradient elution was performed using methanol as mobile phase B and 0.5% formic acid water containing 5 mmol·L−1 ammonium acetate as mobile phase A. Samples were analyzed by means of multiple reaction monitoring (MRM) through the mass separation by Kinetex®C18 column. The detection limits and quantization limits for the 13 antibiotics were 0.05—1.66 ng·L−1 and 0.17—5.52 ng·L−1, respectively. The recoveries ranged from 70.2% to 121.5% with relative standard deviations of 1.1%—13.5%. The method has high sensitivity, high efficiency which can be used for simultaneous determination of antibiotics residues in source water of drinking water sources at trace level. The method was successfully applied to analysis of antibiotics residue in source water in Xiamen. 7 antibiotics were detected, and the concentrations ranged from not detected to 32.6 ng·L−1. -
表 1 MRM 模式下13种抗生素的质谱参数
Table 1. MS parameters in multiple reaction monitoring model for 13 antibiotics
化合物
Compound母离子
Parent
ion子离子
Daughter
ion保留时间/min
Retention
time去簇电压/V
Declustering
potential入口电压/V
Entrance
voltage碰撞能/eV
Collision
energy出口电压/V
Export
voltageOxytetracycline 461 426 4.10 45 8 25 17 (土霉素,OTC) 444* 45 8 25 17 Tetracycline 445 427 3.64 85 8 25 13 (四环素,TC) 410* 85 8 25 13 Chlortetracycline 479 444 5.06 51 9 26 20 (金霉素,CTC) 462* 51 9 26 20 Roxithromycin 837 679* 7.21 60 4.05 40 14.2 (罗红霉素,RTM) 158 60 4.05 40 14.2 Azithromycin 749.3 158 5.75 85 9 45 7 (阿奇霉素,AZM) 591* 85 9 45 7 Erythromycin 734 576* 6.59 50 7 35 14.2 (红霉素,ETM) 158 50 7 35 14.2 Sulfadiazine 251 156.1* 2.69 46 5.5 23 2 (磺胺嘧啶,SDZ) 91.9 46 5.5 35 2 Sulfamethazine 279 186.1* 4.15 46 6 23 2 (磺胺二甲嘧啶,SMZ) 124 72 10 23 10 Sulfamethoxazole 253.9 92.1 4.47 41 5.5 37 2 (磺胺甲噁唑,SMX) 155.9* 77 10 23 29 Ofloxacin 362.2 302* 4.02 59 5.8 26 16 (氧氟沙星,OFL) 233.1 59 5.8 33 11 Ciprofloxacin 332.2 314* 4.23 65 7 35 2 (环丙沙星,CIP) 245 65 7 35 2 Enrofloxacin 360.1 342.2* 4.32 64 7 37 4 (恩诺沙星,ENR) 245.1 64 7 37 4 Difloxacin 400 356* 4.56 43 12 27 5 (二氟沙星,DIF) 299 43 12 27 5 注:*为定量离子. The characterisitic ions asterisk are used for quantification. 表 2 上样体积和洗脱液体积对回收率的影响(%)
Table 2. Recoveries of 13 antibiotics with different sample volumes and eluent volumes(%)
化合物
Compound上样体积Sample volumes 洗脱液体积Eluent volumes 500 mL 1000 mL 4 mL 6 mL 8 mL 10 mL OTC 122.5 87.4 72.4 106.0 108.2 115.0 TC 91.1 64.0 73.0 86.0 97.4 95.3 CTC 74.1 80.9 78.5 74.8 70.4 71.8 RTM 105.5 65.6 68.5 110.8 117.8 84.0 AZM 67.5 68.5 65.4 94.2 114.0 108.6 ETM 68.2 40.1 39.1 71.4 76.5 71.2 SDZ 86.5 71.4 49.6 92.8 84.4 107.2 SMZ 92.0 85.2 77.8 86.3 85.1 97.0 SMX 101.2 60.2 68.2 81.3 78.2 71.4 OFL 90.4 69.2 54.7 94.2 84.9 76.4 CIP 124.8 87.2 46.0 103.9 71.3 75.4 ENR 75.4 64.6 86.1 114.1 102.1 114.4 DIF 94.5 82.7 72.3 94.0 104.6 95.4 表 3 13种抗生素的线性方程、检出限和定量限
Table 3. Linear equations, limits of detections and limits of quantifications of 13 kinds of antibiotics
化合物
Compound线性方程
Linear equation相关系数
Correlation coefficient(R2)检出限/(ng·L−1)
LOD定量限/(ng·L−1)
LOQOTC y=139.71x+67.06 0.9997 1.21 4.02 TC y=206.19x−596.31 0.9996 1.48 5.52 CTC y=162.24x−186.94 0.9997 1.54 5.13 RTM y=205.2x+467.26 0.9969 0.87 2.91 AZM y=464.29x+1292 0.9981 0.05 0.17 ETM y=714.98x+1052.29 0.9991 1.66 5.52 SDZ y=1093.24x+2342.46 0.9965 0.10 0.32 SMZ y=749.91x+1435.55 0.9962 0.08 0.25 SMX y=714.98x+1052.29 0.9991 0.16 0.52 OFL y=921.17x+1229.69 0.9969 0.76 2.52 CIP y=188.34x+197.56 0.9933 1.14 3.81 ENR y=1093.24x+2342.46 0.9965 0.26 0.86 DIF y=835.13x+1290.17 0.9972 1.43 4.76 表 4 13种抗生素在3个加标水平下的加标回收率和相对标准偏差(n=3)
Table 4. Recoveries and relative standard deviations at three spiked levels of 13 antibiotics(n=3)
化合物
Compound加标浓度/(ng·L−1)
Spiked concentration超纯水 Pure water 水源水Source water 回收率/%Recovery RSD/% 回收率/%Recovery RSD/% OTC 2 110.4 1.1 87.4 2.3 20 94.3 9.9 86.1 6.5 100 76.3 8.6 72.5 10.7 TC 2 88.1 4.3 75.6 2.6 20 116.6 6.8 92.8 10.8 100 73.0 9.7 111.5 13.3 CTC 2 89.5 11.4 78.6 9.8 20 117.2 3.2 80.9 5.1 100 79.2 4.9 120.1 5.5 RTM 2 94.8 8.6 73.1 9.9 20 98.3 7.3 75.6 4.4 100 70.5 13.1 101.9 13.5 AZM 2 96.2 7.5 78.5 7.1 20 114.5 9.2 102.9 1.4 100 84.3 12.1 77.0 8.4 ETM 2 75.4 1.2 73.2 3.7 20 94.9 4.8 76.9 8.5 100 97.6 10.3 81.5 12.1 SDZ 2 75.1 12.1 73.1 9.2 20 84.4 11.7 79.6 5.4 100 71.4 12.5 83.9 12.9 SMZ 2 75.3 11.1 79.6 4.2 20 85.2 9.5 70.2 3.4 100 71.5 12.5 77.8 13.1 SMX 2 116.8 0.9 77.5 7.8 20 74.2 12.9 72.2 2.7 100 73.5 10.3 78.2 3.9 OFL 2 105.7 7.9 114.1 12.3 20 84.9 5.7 80.8 5.1 100 77.4 9.8 74.5 9.7 CIP 2 79.2 5.8 84.7 10.9 20 121.5 2.2 89.1 5.9 100 103.9 10.4 71.3 5.6 ENR 2 74.6 11.3 72.9 11.8 20 116.2 7.9 82.6 1.5 100 75.4 3.3 102.6 7.8 DIF 2 73.7 9.3 78.7 10.8 20 88.7 8.9 71.3 2.1 100 107.3 11.5 112.6 12.3 表 5 与其他方法的比较
Table 5. Comparison with other methods
化合物(组分)
Compound( component)检出限/( ng·L-1)
LOD回收率/%
RecoveryRSD/% 参考文献
ReferencesSD、TC、NOF等(三类14种) 0.09—12.3 40.6—127.5 无 [29] AMC、ERY、SMX(五类9种) 0.4—0.8 60.1—104.6 0.7—5.5 [30] TMP、CIP、CTC等(五类10种) 3.0—16.0 71—105 <15 [31] CFX、LIN、RTM等(五类15种) 0.19—1.09 87—170 无 [32] CLR、ROX、AZM等(六类18种) 0.8—45.0 51.0—94.0 3.9—10.6 [33] OTC、ENR、DIF等(四类13种) 0.05—1.66 70.2—121.5 1.1—13.5 本研究 -
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