喹賽多在豬、雞和鯉可食性組織中的殘留消除研究
發(fā)布時(shí)間：2018-09-07 16:24
【摘要】：喹賽多作為喹嗯啉類新藥,對(duì)畜禽及水產(chǎn)品中常見病原菌有良好的抑菌作用,并且能夠提高飼料轉(zhuǎn)化率,促進(jìn)機(jī)體生長(zhǎng)。與同類藥物相比,喹賽多具有安全性更高、毒副作用更低的特點(diǎn)。而作為食品動(dòng)物用藥,對(duì)其安全性評(píng)價(jià)是新藥開發(fā)的重要內(nèi)容。獸藥殘留是影響食品安全的主要因素,但是關(guān)于喹賽多在畜禽及水產(chǎn)品中的殘留消除研究并沒有完全清楚。目前國(guó)際上公認(rèn)的可食性組織包括肝、腎、肌肉、脂肪,而在我國(guó),除了肝、腎、肌肉和脂肪外,主要的可食性組織還有心、肺、胃、大腸和小腸。目前關(guān)于喹賽多的殘留消除研究已在畜禽的肝、腎、肌肉、脂肪中開展,但是喹賽多在心、肺、胃、大腸和小腸中的殘留消除研究仍未見報(bào)道。本課題以豬、雞和鯉魚為研究對(duì)象,建立了喹賽多及其5種主要代謝產(chǎn)物在各可食性組織中殘留檢測(cè)的高效液相色譜方法,并對(duì)這些化合物的殘留消除規(guī)律進(jìn)行研究。本研究表明,喹賽多用于豬、雞和鯉之后,吸收和消除迅速。通過本研究進(jìn)一步確定了喹賽多在豬和雞體內(nèi)的殘留靶組織是腎臟,殘留標(biāo)示物是Cyl；在鯉體內(nèi)的殘留靶組織是胃腸,殘留標(biāo)示物是Cy1。闡明了喹賽多在動(dòng)物體內(nèi)的安全性,為食品安全評(píng)價(jià)提供理論依據(jù)和技術(shù)支持。1殘留檢測(cè)方法的建立本實(shí)驗(yàn)建立了喹賽多(Cy0)、脫二氧喹賽多(Cyl)、N4-脫一氧喹賽多(Cy2)、N-(喹VA啉-2-甲基)-氰乙酰肼(Cy4)、喹嗯啉-2-羧酸(Cy6)和2-氰基-N'-(N1-氧喹VA啉-2-亞甲基)乙酰肼(Cy9)六種化合物在豬和雞的肝臟、腎臟、肌肉、脂肪、心、肺、胃、大腸和小腸9種可食性組織：鯉魚的肝臟、腎臟、肌肉、脂肪、皮膚和胃腸道6種可食性組織中的殘留檢測(cè)方法。各組織依次通過乙酸乙酯提取、體積比為1：50：10：39的甲酸：甲醇：乙腈：水復(fù)合試劑提取、正己烷去脂和親水親脂平衡型共聚物(HLB)小柱凈化,最后經(jīng)體積比為15：85的乙腈：水混合試劑復(fù)溶,320 nm紫外波長(zhǎng)下通過高效液相色譜進(jìn)行檢測(cè)。該方法下Cy0、Cy1和Cy6在豬和雞的肌肉、心臟、肺臟及魚的肌肉、皮膚和胃腸的定量限為15μg/kg,在豬和雞的肝、腎、脂肪、胃、大腸和小腸及魚肝、腎和脂肪中的定量限為20μg/kg;Cy2、Cy4和Cy9在豬和雞的肌肉、心臟、肺臟及魚的肌肉、皮膚和胃腸的定量限為20μg/kg,在豬和雞的肝、腎、脂肪、胃、大腸和小腸及魚肝、腎和脂肪中的定量限為40μg/kg。添加不同定量限水平上濃度的藥物,回收率在均在60%以上,且日間變異系數(shù)在12%以下。農(nóng)業(yè)部規(guī)定殘留檢測(cè)方法日間相對(duì)標(biāo)準(zhǔn)偏差17%-21%,本實(shí)驗(yàn)建立的方法滿足該要求,能用于喹賽多及其代謝產(chǎn)物的定量分析。2喹賽多在豬、雞和鯉體內(nèi)的殘留消除研究健康三元雜交豬25頭、20日齡科寶肉雞30羽和健康鯉魚30尾,各分成5組。連續(xù)飼喂添加200 mg/kg喹賽多的飼料2周,停藥后于不同時(shí)間點(diǎn)宰殺一組,收肝臟、腎臟、肌肉、脂肪、心、肺、胃、大腸和小腸。按上述方法對(duì)組織中藥物的含量進(jìn)行測(cè)定,結(jié)果如下：豬：停藥6 h,除脂肪外各組織均檢測(cè)到原形和QCA,藥物濃度范圍分別為21.8-66.3μg/kg和22.4-56.9μg/kg;各組織中均檢測(cè)出Cyl,濃度范圍是20.4-66.0μg/kg,原形和QCA在豬體內(nèi)消除迅速。停藥1 d,各組織中原形均消除至定量限以下,腎臟和肺臟中檢測(cè)出QCA,濃度分別為22.3 μg/kg和25.1 μg/kg;肝、腎、肺和小腸中檢測(cè)到Cyl,濃度范圍是20.8-44.2μg/kg,腎臟最高。停藥3 d,各組織中QCA均消除至定量限以下,只有腎臟中能檢測(cè)到少量的Cyl。停藥7d各組織中Cyl均低于定量限。雞：肌肉和脂肪沒有檢測(cè)到任何代謝產(chǎn)物。停藥6 h,原形藥物只在肝臟、腎臟、小腸、心、肺和胃中檢測(cè)出,濃度范圍是21.4-67.2μg/kg,腎臟最高；肝臟、腎臟、心臟、肺臟和小腸中均檢測(cè)到QCA,濃度范圍為24.7-66.8μg/kg,腎臟中最高；肝臟、腎臟、心、肺、大腸和小腸檢測(cè)出Cyl,濃度范圍是32.8-65.6μg/kg。停藥1 d,原形和QCA僅在腎臟中檢測(cè)出,濃度分別為34.1和32.5μg/kg;在肝、腎和肺中檢測(cè)出Cyl,濃度分別為32.0、47.4和23.0μg/kg。停藥3 d,僅在腎中檢測(cè)出少量的Cy1。停藥5 d,各組織中檢測(cè)不到任何代謝產(chǎn)物。鯉：停藥6 h,各組織中除原形、脫二氧喹賽多和QCA外,還在皮膚和胃腸中檢測(cè)出Cy4,在腎臟、肌肉、脂肪、皮膚和胃腸中檢測(cè)出原形,濃度范圍為15.2-25.5 μg/kg腎臟居多；肝、腎、皮膚和胃腸中檢測(cè)到QCA,濃度范圍為20.2-36.1μg/kg各組織中均檢測(cè)到Cyl,濃度范圍為32.4-40.8μg/kg,胃腸最高。停藥1 d,各組織中的原形和QCA均消除至定量限以下；除脂肪外各組織中均檢測(cè)到Cy1,濃度范圍20.5-36.8μg/kg,胃腸最高。停藥3 d,僅胃腸道有少量的Cy1。停藥7d各組織中檢測(cè)不到任何代謝產(chǎn)物。綜上所述,本實(shí)驗(yàn)首次建立喹賽多及其5種主要主要代謝產(chǎn)物在豬和雞9種可食性組織,魚6種可食性組織中的殘留檢測(cè)方法,同時(shí),首次闡明了喹賽多及其代謝產(chǎn)物在這些組織中的消除規(guī)律,其研究結(jié)果為指導(dǎo)臨床合理用藥、藥物安全性評(píng)價(jià)和殘留標(biāo)示物的確定提供了科學(xué)依據(jù)。
[Abstract]:As a new quinoxaline drug, quinoxaldol has a good bacteriostatic effect on common pathogenic bacteria in livestock, poultry and aquatic products, and can improve feed conversion rate and promote the growth of the body. Compared with the same drugs, quinoxaldol has higher safety and lower side effects. As a food animal drug, its safety evaluation is a new drug development. Veterinary drug residue is a major factor affecting food safety, but the study on the elimination of quinacetin residue in livestock, poultry and aquatic products is not entirely clear. Lung, stomach, large intestine and small intestine. At present, the study on the elimination of quetiapine has been carried out in the liver, kidney, muscle and fat of livestock and poultry. However, the study on the residual elimination of quinazadiam in heart, lung, stomach, large intestine and small intestine has not been reported. In this study, quinazo and its 5 main metabolites were found in pigs, chickens and carps. The residues in the tissues were detected by high performance liquid chromatography, and the residue elimination rule of these compounds was studied. This study shows that quetiapine can rapidly absorb and eliminate after being used in pigs, chickens and carps. Through this study, it is further confirmed that the residual target tissue of quetial in pigs and chickens is the kidneys, and the residual marker is Cyl. The residual target tissue in vivo is the gastrointestinal tract, and the residual marker is Cy1. The safety of quinacetin in vivo was clarified, which provides theoretical basis and technical support for food safety evaluation. 1 The method of residue detection was established. Cy0, Cyl, N4-deoxyquinacetin (Cy2), N-(quinoVAline-2-methyl)-cyanoethyl. Hydrazine (Cy4), quinoline -2- carboxylic acid (Cy6) and 2- cyano -N'- (N1- oxoquine VA VA -2- Ya Jiaji) acetyl hydrazine (Cy9) six compounds in pig and chicken liver, kidney, muscle, fat, heart, lung, stomach, large intestine and small intestine 9 kinds of edible tissue: carp liver, kidney, muscle, fat, skin and gastrointestinal 6 kinds of edible tissue residues detection method. The tissues were extracted by ethyl acetate with a volume ratio of 1:50:10:39, formic acid: methanol: acetonitrile: water complex reagent extraction, n-hexane degreasing and hydrophilic lipophilic equilibrium copolymer (HLB) column purification, and finally re-dissolved by acetonitrile: water mixture reagent with a volume ratio of 15:85, and carried out by high performance liquid chromatography at 320 nm ultraviolet wavelength. The limit of quantification for Cy0, Cy1 and Cy6 in pigs, chickens * muscles, heart, lungs and fish muscle, skin and gastrointestinal was 15 * g/kg, and the limit of quantification in pigs, chickens, liver, kidney, fat, stomach, large intestine and small intestine and liver, kidney and fat was 20 * g/kg; Cy2, Cy4 and Cy9 in muscle, heart, lungs and fish muscles, skin and stomach of pigs and chickens. The limit of quantification was 20 * g/kg, and the quantitation limit for liver, kidney, fat, stomach, large intestine, small intestine, liver, kidney and fat of pigs and chickens was 40 g/kg.. The recoveries were over 60% and the coefficient of variation of day was below 12% when adding different quantitation limits. The Ministry of agriculture stipulated that the relative standard deviation of residue detection method was 17%-21%. The established method can meet the requirement and can be used for the quantitative analysis of quetiapine and its metabolites. The elimination of.2 * quetiapine residues in pigs, chickens and carp * three healthy 25 crossbred pigs, 30 days of 20 days old Cobb broilers and 30 healthy carp Cyprinus carpio were divided into 5 groups. Continuous feeding of 200 mg/kg quetiapine feed for 2 weeks, after withdrawal of different drugs. At the time point, a group was slaughtered, and liver, kidney, muscle, fat, heart, lung, stomach, large intestine and small intestine were collected. * the contents of the drugs in the tissues were determined according to the above methods. The results were as follows: pigs were stopped for 6 h, and the original and QCA were detected in all tissues except fat. The concentrations of drugs ranged from 21.8-66.3 to g/kg and 22.4-56.9 g/kg respectively, and C was detected in all tissues. YL, the concentration range was 20.4-66.0 * g/kg, the original shape and QCA were eliminated rapidly in pigs. After stopping 1 D, the prototypes of all tissues were removed below the quantitation limit, and QCA in the kidneys and lungs was detected. The concentrations were 22.3 g/kg and 25.1 g/kg respectively. Cyl was detected in the liver, kidney, lung and small intestine, the concentration range was 20.8-44.2, g/kg, the kidney was the highest, the drug withdrawal was 3, and the tissues were different. Chicken: No metabolites were detected in muscle and fat. Within 6 hours, prototype drugs were detected only in liver, kidney, small intestine, heart, lung and stomach. The concentration range was 21.4-67.2 ug/kg, the highest in kidney. QCA was detected in kidney, heart, lung and small intestine, the concentration range was 24.7-66.8 ug/kg, the highest in kidney; Cyl was detected in liver, kidney, heart, lung, large intestine and small intestine, the concentration range was 32.8-65.6 ug/kg. Cy4 was detected in the skin and gastrointestinal tract, besides prototype, deoxyquinocetone and QCA. Cy4 was detected in the kidney, muscle, fat, skin and gastrointestinal tract. QCA was detected in liver, kidney, skin and gastrointestinal tract. Cyl was detected in 20.2-36.1 ug/kg tissues. The concentration ranged from 32.4-40.8 ug/kg, and the gastrointestinal tract was the highest. 36.8 g/kg, the highest gastrointestinal tract. 3 D was stopped. Only a small amount of Cy1. was stopped in the gastrointestinal tract. NO metabolites were detected in all tissues of 7D. In summary, this experiment established for the first time that quinazo and its 5 main metabolites * 9 kinds of edible tissues in pigs and chickens, and residue detection methods in 6 edible tissues. The elimination of polymorphisms and their metabolites in these tissues provides a scientific basis for clinical rational drug use, drug safety evaluation and determination of residual markers.
【學(xué)位授予單位】：華中農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S859.84
，
本文編號(hào)：2228786
[Abstract]:As a new quinoxaline drug, quinoxaldol has a good bacteriostatic effect on common pathogenic bacteria in livestock, poultry and aquatic products, and can improve feed conversion rate and promote the growth of the body. Compared with the same drugs, quinoxaldol has higher safety and lower side effects. As a food animal drug, its safety evaluation is a new drug development. Veterinary drug residue is a major factor affecting food safety, but the study on the elimination of quinacetin residue in livestock, poultry and aquatic products is not entirely clear. Lung, stomach, large intestine and small intestine. At present, the study on the elimination of quetiapine has been carried out in the liver, kidney, muscle and fat of livestock and poultry. However, the study on the residual elimination of quinazadiam in heart, lung, stomach, large intestine and small intestine has not been reported. In this study, quinazo and its 5 main metabolites were found in pigs, chickens and carps. The residues in the tissues were detected by high performance liquid chromatography, and the residue elimination rule of these compounds was studied. This study shows that quetiapine can rapidly absorb and eliminate after being used in pigs, chickens and carps. Through this study, it is further confirmed that the residual target tissue of quetial in pigs and chickens is the kidneys, and the residual marker is Cyl. The residual target tissue in vivo is the gastrointestinal tract, and the residual marker is Cy1. The safety of quinacetin in vivo was clarified, which provides theoretical basis and technical support for food safety evaluation. 1 The method of residue detection was established. Cy0, Cyl, N4-deoxyquinacetin (Cy2), N-(quinoVAline-2-methyl)-cyanoethyl. Hydrazine (Cy4), quinoline -2- carboxylic acid (Cy6) and 2- cyano -N'- (N1- oxoquine VA VA -2- Ya Jiaji) acetyl hydrazine (Cy9) six compounds in pig and chicken liver, kidney, muscle, fat, heart, lung, stomach, large intestine and small intestine 9 kinds of edible tissue: carp liver, kidney, muscle, fat, skin and gastrointestinal 6 kinds of edible tissue residues detection method. The tissues were extracted by ethyl acetate with a volume ratio of 1:50:10:39, formic acid: methanol: acetonitrile: water complex reagent extraction, n-hexane degreasing and hydrophilic lipophilic equilibrium copolymer (HLB) column purification, and finally re-dissolved by acetonitrile: water mixture reagent with a volume ratio of 15:85, and carried out by high performance liquid chromatography at 320 nm ultraviolet wavelength. The limit of quantification for Cy0, Cy1 and Cy6 in pigs, chickens * muscles, heart, lungs and fish muscle, skin and gastrointestinal was 15 * g/kg, and the limit of quantification in pigs, chickens, liver, kidney, fat, stomach, large intestine and small intestine and liver, kidney and fat was 20 * g/kg; Cy2, Cy4 and Cy9 in muscle, heart, lungs and fish muscles, skin and stomach of pigs and chickens. The limit of quantification was 20 * g/kg, and the quantitation limit for liver, kidney, fat, stomach, large intestine, small intestine, liver, kidney and fat of pigs and chickens was 40 g/kg.. The recoveries were over 60% and the coefficient of variation of day was below 12% when adding different quantitation limits. The Ministry of agriculture stipulated that the relative standard deviation of residue detection method was 17%-21%. The established method can meet the requirement and can be used for the quantitative analysis of quetiapine and its metabolites. The elimination of.2 * quetiapine residues in pigs, chickens and carp * three healthy 25 crossbred pigs, 30 days of 20 days old Cobb broilers and 30 healthy carp Cyprinus carpio were divided into 5 groups. Continuous feeding of 200 mg/kg quetiapine feed for 2 weeks, after withdrawal of different drugs. At the time point, a group was slaughtered, and liver, kidney, muscle, fat, heart, lung, stomach, large intestine and small intestine were collected. * the contents of the drugs in the tissues were determined according to the above methods. The results were as follows: pigs were stopped for 6 h, and the original and QCA were detected in all tissues except fat. The concentrations of drugs ranged from 21.8-66.3 to g/kg and 22.4-56.9 g/kg respectively, and C was detected in all tissues. YL, the concentration range was 20.4-66.0 * g/kg, the original shape and QCA were eliminated rapidly in pigs. After stopping 1 D, the prototypes of all tissues were removed below the quantitation limit, and QCA in the kidneys and lungs was detected. The concentrations were 22.3 g/kg and 25.1 g/kg respectively. Cyl was detected in the liver, kidney, lung and small intestine, the concentration range was 20.8-44.2, g/kg, the kidney was the highest, the drug withdrawal was 3, and the tissues were different. Chicken: No metabolites were detected in muscle and fat. Within 6 hours, prototype drugs were detected only in liver, kidney, small intestine, heart, lung and stomach. The concentration range was 21.4-67.2 ug/kg, the highest in kidney. QCA was detected in kidney, heart, lung and small intestine, the concentration range was 24.7-66.8 ug/kg, the highest in kidney; Cyl was detected in liver, kidney, heart, lung, large intestine and small intestine, the concentration range was 32.8-65.6 ug/kg. Cy4 was detected in the skin and gastrointestinal tract, besides prototype, deoxyquinocetone and QCA. Cy4 was detected in the kidney, muscle, fat, skin and gastrointestinal tract. QCA was detected in liver, kidney, skin and gastrointestinal tract. Cyl was detected in 20.2-36.1 ug/kg tissues. The concentration ranged from 32.4-40.8 ug/kg, and the gastrointestinal tract was the highest. 36.8 g/kg, the highest gastrointestinal tract. 3 D was stopped. Only a small amount of Cy1. was stopped in the gastrointestinal tract. NO metabolites were detected in all tissues of 7D. In summary, this experiment established for the first time that quinazo and its 5 main metabolites * 9 kinds of edible tissues in pigs and chickens, and residue detection methods in 6 edible tissues. The elimination of polymorphisms and their metabolites in these tissues provides a scientific basis for clinical rational drug use, drug safety evaluation and determination of residual markers.
【學(xué)位授予單位】：華中農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S859.84
，
本文編號(hào)：2228786
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