高效液相色谱-串联质谱法测定乳制品中的莫奈太尔及其代谢物
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摘要
建立测定乳制品中莫奈太尔及其代谢物的高效液相色谱-串联质谱法。试样加水-饱和氯化钠-乙腈溶液提取,正己烷净化,经Inertsil C_8(2.1 mm×100 mm,3μm)色谱柱分离,以甲醇-0.5 mmol/L乙酸铵溶液为流动相进行梯度洗脱,采用电喷雾离子源串联质谱,在负离子扫描方式下以多反应监测模式检测,外标法定量。结果表明:莫奈太尔及其代谢物在0.1～5.0μg/L范围内线性关系良好,定量限为2.0μg/kg。在3个加标水平下的平均回收率为79.5%～102.9%,相对标准偏差为2.0%～5.3%。该方法操作简便、快速、准确、灵敏度高、抗干扰能力强、回收率和重复性良好,适合于乳制品中莫奈太尔及其代谢物的测定。
A method was developed for the determination of monepantel and its metabolite residues in dairy products by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). The sample was ultrasonically extracted with a mixture of saturated sodium chloride solution and acetonitrile, and then the extract was puri?ed by hexane.The target compounds were separated on an inertsil C_8 column(2.1 mm × 100 mm, 3 μm) using a gradient elution program with a mobile phase composed of methanol and 0.5 mmol/L ammonium acetate, and detected by tandem mass spectrometry using negative electrospray ionization in multiple reaction monitoring(MRM) mode. The quanti?cation of monepantel and its metabolite residues was performed by the external standard method. The calibration curves showed a good linearity within the concentration range of 0.1–5.0 μg/L and the limit of quantitation(LOQ) was 2.0 μg/kg.The recoveries for dairy products at three spiked levels were in the range of 79.5%–102.9% with relative standard deviations(RSDs) between 2.0% and 5.3%. With the advantages of simplicity, rapidity, accuracy, high sensitivity,strong anti-interference capacity and good recovery and repeatability, the method could be suitable for the analysis of monepantel and its metabolite residues in dairy products.
A method was developed for the determination of monepantel and its metabolite residues in dairy products by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). The sample was ultrasonically extracted with a mixture of saturated sodium chloride solution and acetonitrile, and then the extract was puri?ed by hexane.The target compounds were separated on an inertsil C_8 column(2.1 mm × 100 mm, 3 μm) using a gradient elution program with a mobile phase composed of methanol and 0.5 mmol/L ammonium acetate, and detected by tandem mass spectrometry using negative electrospray ionization in multiple reaction monitoring(MRM) mode. The quanti?cation of monepantel and its metabolite residues was performed by the external standard method. The calibration curves showed a good linearity within the concentration range of 0.1–5.0 μg/L and the limit of quantitation(LOQ) was 2.0 μg/kg.The recoveries for dairy products at three spiked levels were in the range of 79.5%–102.9% with relative standard deviations(RSDs) between 2.0% and 5.3%. With the advantages of simplicity, rapidity, accuracy, high sensitivity,strong anti-interference capacity and good recovery and repeatability, the method could be suitable for the analysis of monepantel and its metabolite residues in dairy products.
引文
[1]刘慧琳,倪天鸿,周凯文,等.分子印迹固相萃取-高效液相色谱法检测奶粉中的双氰胺[J].食品科学,2017,38(20):203-208.DOI:10.7506/spkx1002-6630-201720029.
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[15]HOSKING B C,STEIN P A,MOSIMANN D,et al.Dose determination studies for monepantel,an amino-acetonitrile derivative,against fourth stage gastro-intestinal nematode larvae infecting sheep[J].Veterinary Parasitology,2008,157(1):72-80.DOI:10.1016/j.vetpar.2008.07.014.
[16]ABONGWA M,MARJANOVIC D S,TIPTON J G,et al.Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum[J].International Journal for Parasitology Drugs and Drug Resistance,2017,8(1):36-42.DOI:10.1016/j.ijpddr.2017.12.001.
[17]BALLENT M,VIVIANI P,IMPERIALE F,et al.Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows[J].Journal of Veterinary Pharmacology and Therapeutics,2018,41(2):292-300.DOI:10.1111/jvp.12466.
[18]OLIVEIRA P A,RIET-CORREA B,ESTIMA-SILVA P,et al.Multiple anthelmintic resistance in Southern Brazil sheep flocks[J].Revista Brasileira de Parasitologia Veterinária,2017,26(4):427-432.DOI:10.1590/S1984-29612017058.
[19]HODGSON B,MULVANEY C J.Resistance to a triple-combination anthelmintic in Trichostrongylus spp.on a commercial sheep farm in New Zealand[J].New Zealand Veterinary Journal,2017,65(5):277-281.DOI:10.1080/00480169.2017.1333468.
[20]BAGNALL N H,RUFFELL A,RAZA A,et al.Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus[J].International Journal for Parasitology Drugs and Drug Resistance,2017,7(2):236-240.DOI:10.1016/j.ijpddr.2017.05.001.
[21]LIFSCHITZ A,LANUSSE C,ALVAREZ L.Host pharmacokinetics and drug accumulation of anthelmintics within target helminth parasites of ruminants[J].New Zealand Veterinary Journal,2017,65(4):176-184.DOI:10.1080/00480169.2017.1317222.
[22]SUAREZ V H,MARTíNEZ G M,VI?ABAL A E,et al.Epidemiology and effect of gastrointestinal nematodes on dairy goats in Argentina[J].Onderstepoort Journal of Veterinary Research,2017,84(1):1-5.DOI:10.4102/ojvr.v84i1.1240.
[23]HESS J,PATRA M,JABBAR A,et al.Assessment of the nematocidal activity of met allocenyl analogues of monepantel[J].Dalton Transactions,2016,45(44):17662-17671.DOI:10.1039/c6dt03376h.
[24]MAHNKE H,BALLENT M,BAUMANN S,et al.The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows[J].Drug Metabolism and Disposition,2016,44(5):700-708.DOI:10.1124/dmd.115.068940.
[25]BALLENT M,VIRKEL G,MATéL,et al.Hepatic biotransformation pathways and ruminal metabolic stability of the novel anthelminticmonepantel in sheep and cattle[J].Journal of Veterinary Pharmacology and Therapeutics,2016,39(5):488-496.DOI:10.1111/jvp.12296.
[26]CHAGAS A C,DOMINGUES L F,GAíNZA Y A,et al.Target selected treatment with levamisole to control the development of anthelmintic resistance in a sheep flock[J].Parasitology Research,2016,115(3):1131-1139.DOI:10.1007/s00436-015-4844-x.
[27]BARTLEY D J,DEVIN L,NATH M,et al.Selection and characterisation of monepantel resistance in Teladorsagia circumcincta isolates[J].International Journal for Parasitology Drugs and Drug Resistance,2015,5(2):69-76.DOI:10.1016/j.ijpddr.2015.05.001.
[28]VAN DEN BROM R,MOLL L,KAPPERT C,et al.Haemonchus contortus resistance to monepantel in sheep[J].Veterinary Parasitology,2015,209(3/4):278-280.DOI:10.1016/j.vetpar.2015.02.026.
[29]BAUR R,BEECH R,SIGEL E,et al.Monepantel irreversibly binds to and opens Haemonchus contortus MPTL-1 and Caenorhabditis elegans ACR-20 receptors[J].Molecular Pharmacology,2015,87(1):96-102.DOI:10.1124/mol.114.095653.
[30]2013年欧盟发布对37/2010进行修订的5个法规[EB/OL].http://news.foodmate.net/2013/05/233299.html.
[31]STUCHLíKOVáL,JIRáSKO R,VOK?áL I,et al.Investigation of the metabolism of monepantel in ovine hepatocytes by UHPLC/MS/MS[J].Analytical and Bioanalytical Chemistry,2013,405(5):1705-1712.DOI:10.1007/s00216-012-6584-4.
[32]杨家峰,段青源,钟惠英,等.液相色谱法测定水产饲料中15种磺胺类药物[J].饲料检测,2009(7):44-48.DOI:10.13557/j.cnki.issn1002-2813.2009.07.025.
[2]苗水红.寄生虫病的危害及其药物应用存在的问题[J].湖北畜牧兽医,2014,35(1):37-38.DOI:10.16733/j.cnki.issn1007-273x.2014.01.020.
[3]崔磊,黄米妮,张力,等.功能性奶粉国内市场现状及发展趋势分析[J].江苏农业科学,2011,39(4):8-11.
[4]吴映璇,林峰,谢敏玲,等.高效液相色谱-串联质谱法测定乳制品中高氯酸盐[J].中国食品卫生杂志,2017,29(2):160-164.DOI:10.13590/j.cjfh.2017.02.009.
[5]吴映璇,林峰,姚仰勋.亲水作用色谱-质谱法同时检测鱼肉中链霉素和双氢链霉素残留[J].食品安全质量检测学报,2013,4(5):1467-1472.
[6]林海丹,林峰,张美金,等.高效液相色谱法同时测定动物组织中16种苯并咪唑类药物残留[J].食品科学,2011,32(2):231-236.
[7]徐静,肖珊珊,董伟峰,等.两次液液萃取-气相色谱-质谱联用法测定动物肝脏中左旋咪唑残留[J].色谱,2012,30(9):922-925.DOI:10.3724/SP.J.1123.2012.04030.
[8]王浩,赵丽,杨红梅,等.液相色谱-串联质谱法测定牛奶中35种四环素类、磺胺类、青霉素类、大环内酯类、氯霉素类抗生素残留[J].色谱,2015,33(9):995-1001.DOI:10.3724/SP.J.1123.2015.04046.
[9]陈琳,陈杖榴.大环内酯类抗寄生虫药耐药性研究进展[J].动物医学进展,2005,26(10):9-13.
[10]KAMINSKY R,DUCRAY P,JUNG M,et al.A new class of anthelmintics effective against drug-resistant nematodes[J].Nature,2008,452:176-180.DOI:10.1038/nature06722.
[11]梁先明,李亚菲,曾振灵.兽用抗寄生虫药莫奈太尔的研究进展[J].中国兽药杂志,2014,48(8):61-65.
[12]HESS J,PATRA M,RANGASAMY L,et al.Organomet allic derivatization of the nematocidal drug monepantel leads to promising antiparasitic drug candidates[J].Chemistry,2016,22(46):16602-16612.DOI:10.1002/chem.201602851.
[13]SAGER H,HOSKING B,BAPST B,et al.Efficacy of the aminoacetonitrile derivative,monepantel,against experimental and natural adult stage gastro-intestinal nematode infections in sheep[J].Veterinary Parasitology,2009,159(1):49-54.DOI:10.1016/j.vetpar.2008.10.006.
[14]KAMINSKY R,MOSIMANN D,SAGER H,et al.Determination of the effective dose rate for monepantel(AAD 1566)against adult gastro-intestinal nematodes in sheep[J].International Journal for Parasitology,2009,39(4):443-446.DOI:10.1016/j.ijpara.2008.09.009.
[15]HOSKING B C,STEIN P A,MOSIMANN D,et al.Dose determination studies for monepantel,an amino-acetonitrile derivative,against fourth stage gastro-intestinal nematode larvae infecting sheep[J].Veterinary Parasitology,2008,157(1):72-80.DOI:10.1016/j.vetpar.2008.07.014.
[16]ABONGWA M,MARJANOVIC D S,TIPTON J G,et al.Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors from Ascaris suum and Oesophagostomum dentatum[J].International Journal for Parasitology Drugs and Drug Resistance,2017,8(1):36-42.DOI:10.1016/j.ijpddr.2017.12.001.
[17]BALLENT M,VIVIANI P,IMPERIALE F,et al.Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows[J].Journal of Veterinary Pharmacology and Therapeutics,2018,41(2):292-300.DOI:10.1111/jvp.12466.
[18]OLIVEIRA P A,RIET-CORREA B,ESTIMA-SILVA P,et al.Multiple anthelmintic resistance in Southern Brazil sheep flocks[J].Revista Brasileira de Parasitologia Veterinária,2017,26(4):427-432.DOI:10.1590/S1984-29612017058.
[19]HODGSON B,MULVANEY C J.Resistance to a triple-combination anthelmintic in Trichostrongylus spp.on a commercial sheep farm in New Zealand[J].New Zealand Veterinary Journal,2017,65(5):277-281.DOI:10.1080/00480169.2017.1333468.
[20]BAGNALL N H,RUFFELL A,RAZA A,et al.Mutations in the Hco-mptl-1 gene in a field-derived monepantel-resistant isolate of Haemonchus contortus[J].International Journal for Parasitology Drugs and Drug Resistance,2017,7(2):236-240.DOI:10.1016/j.ijpddr.2017.05.001.
[21]LIFSCHITZ A,LANUSSE C,ALVAREZ L.Host pharmacokinetics and drug accumulation of anthelmintics within target helminth parasites of ruminants[J].New Zealand Veterinary Journal,2017,65(4):176-184.DOI:10.1080/00480169.2017.1317222.
[22]SUAREZ V H,MARTíNEZ G M,VI?ABAL A E,et al.Epidemiology and effect of gastrointestinal nematodes on dairy goats in Argentina[J].Onderstepoort Journal of Veterinary Research,2017,84(1):1-5.DOI:10.4102/ojvr.v84i1.1240.
[23]HESS J,PATRA M,JABBAR A,et al.Assessment of the nematocidal activity of met allocenyl analogues of monepantel[J].Dalton Transactions,2016,45(44):17662-17671.DOI:10.1039/c6dt03376h.
[24]MAHNKE H,BALLENT M,BAUMANN S,et al.The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows[J].Drug Metabolism and Disposition,2016,44(5):700-708.DOI:10.1124/dmd.115.068940.
[25]BALLENT M,VIRKEL G,MATéL,et al.Hepatic biotransformation pathways and ruminal metabolic stability of the novel anthelminticmonepantel in sheep and cattle[J].Journal of Veterinary Pharmacology and Therapeutics,2016,39(5):488-496.DOI:10.1111/jvp.12296.
[26]CHAGAS A C,DOMINGUES L F,GAíNZA Y A,et al.Target selected treatment with levamisole to control the development of anthelmintic resistance in a sheep flock[J].Parasitology Research,2016,115(3):1131-1139.DOI:10.1007/s00436-015-4844-x.
[27]BARTLEY D J,DEVIN L,NATH M,et al.Selection and characterisation of monepantel resistance in Teladorsagia circumcincta isolates[J].International Journal for Parasitology Drugs and Drug Resistance,2015,5(2):69-76.DOI:10.1016/j.ijpddr.2015.05.001.
[28]VAN DEN BROM R,MOLL L,KAPPERT C,et al.Haemonchus contortus resistance to monepantel in sheep[J].Veterinary Parasitology,2015,209(3/4):278-280.DOI:10.1016/j.vetpar.2015.02.026.
[29]BAUR R,BEECH R,SIGEL E,et al.Monepantel irreversibly binds to and opens Haemonchus contortus MPTL-1 and Caenorhabditis elegans ACR-20 receptors[J].Molecular Pharmacology,2015,87(1):96-102.DOI:10.1124/mol.114.095653.
[30]2013年欧盟发布对37/2010进行修订的5个法规[EB/OL].http://news.foodmate.net/2013/05/233299.html.
[31]STUCHLíKOVáL,JIRáSKO R,VOK?áL I,et al.Investigation of the metabolism of monepantel in ovine hepatocytes by UHPLC/MS/MS[J].Analytical and Bioanalytical Chemistry,2013,405(5):1705-1712.DOI:10.1007/s00216-012-6584-4.
[32]杨家峰,段青源,钟惠英,等.液相色谱法测定水产饲料中15种磺胺类药物[J].饲料检测,2009(7):44-48.DOI:10.13557/j.cnki.issn1002-2813.2009.07.025.