Pharmacokinetics of cyadox （CYX） and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox （BDCYX）, cyadox-1-monoxide （CYX-1-O） and quinoxaline-2-carboxylic acid （QCA）, th...Pharmacokinetics of cyadox （CYX） and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox （BDCYX）, cyadox-1-monoxide （CYX-1-O） and quinoxaline-2-carboxylic acid （QCA）, three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox （CYX） was administered to 8 healthy cross-bread swine intravenously （i.v.） and orally （p.o.） at a dosage of 1 mg kg^-1 body weight and 40 mg kg-1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve （AUC0-∞） were （0.38±0.03） lag mL-I h （CYX）, （0.018±0.002） lag mL-1 h （BDCYX） and （0.17±0.02） lag mL^-1 h （CYX- 1-O）, respectively. The terminal elimination half-lives （t1/2kz） were determined to be （0.93±0.07） h （CYX）, （1.45±0.04） h （BDCYX）, and （0.92±0.04） h （CYX-1-O）, respectively. Steady-state distribution volume （Vss） of （2.14±0.11） L kg^-1 and total body clearance （CL） of （2.84±0.19） L h^-1 kg^-1 were determined for CYX after i.v. dosing. The bioavailability （F） of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations （Cmax） of （1.08±0.06） lag mL^-1 （CYX）, （0.0068~ 0.0004） lag mL-1 （BDCYX） and （0.25~0.03） gg mL-~ （CYX-I-O） were observed at Tmax of 0.033 h （CYX）, 1 h （BDCYX） and 0.033 h （CYX-1-O）, respectively. The main pharmacokinetic parameters after p.o. administration were as follows： AUC0.= were （0.42~0.04） lag mL^-1 h （CYX）, （1.38±0.14） μg mL-1 h （BDCYX）, （0.59±0.02） lag mL-1 h （CYX-1-O） and （1.48＋0.09） lag mL-＇ h （QCA）, respectively, t1/2λz were （4.77±0.33） h （CYX）, （5.77±0.56） h （BDCYX）, （4.12＋0.28） h （CYX-1-O）, and （8.51＋0.39） h （QCA）, respectively. After p.o. administration, CmaxS of （0.033±0.002） μg mL^-1 （CYX）, （0.22±0.03） mg mL^-1 （BDCYX）, （0.089±0.005） μg mL^-1 （CYX-1-O）, and （0.17± 0.01） mg mL^-1 （QCA） were observed at Tmax of（7.38±0.33） h （CYX）, （7.25±0.31） h （BDCYX）, （7.38±0.33） h （CYX-1-O）, and （7.25±0.31） h （QCA）, respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve （AUC0-∞）of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives （t1/2λz） of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.展开更多
150只去势长大仔猪随机分为6组,Ⅰ和Ⅳ组饲喂不含抗菌药的基础日粮,Ⅱ和Ⅴ组基础日粮中添加喹乙醇100m g/kg,Ⅲ和Ⅵ组基础日粮中添加喹赛多100 m g/kg。Ⅳ、Ⅴ和Ⅵ组仔猪灌服1010CFU产肠毒素性大肠杆菌(O139∶K88),Ⅰ、Ⅱ和Ⅲ组仅灌服...150只去势长大仔猪随机分为6组,Ⅰ和Ⅳ组饲喂不含抗菌药的基础日粮,Ⅱ和Ⅴ组基础日粮中添加喹乙醇100m g/kg,Ⅲ和Ⅵ组基础日粮中添加喹赛多100 m g/kg。Ⅳ、Ⅴ和Ⅵ组仔猪灌服1010CFU产肠毒素性大肠杆菌(O139∶K88),Ⅰ、Ⅱ和Ⅲ组仅灌服肉汤。结果表明,喹赛多饲喂猪直肠粪便中大肠杆菌总数和接种的血清型大肠杆菌数与喹乙醇饲喂猪均无显著差异(P>0.05),喹赛多和喹乙醇饲喂猪直肠粪便中接种的血清型大肠杆菌数均低于非药物饲喂猪(P<0.05)。Ⅳ组仔猪感染率为68%;Ⅴ和Ⅵ组感染率均为16%。药物饲喂猪平均日增重显著改善(P<0.05),喹赛多饲喂猪平均日增重高于喹乙醇饲喂猪(P<0.05)。Ⅳ组仔猪平均日增重和饲料转化率分别下降9.6%和8.4%,Ⅵ组仔猪日增重和饲料转化率分别提高11.9%和7.9%,均高于Ⅴ组(4.2%和1.5%)。可见喹赛多不仅对断奶仔猪产肠毒素大肠杆菌感染有显著预防作用,而且还有较好的促进生长和提高饲料转化率作用。展开更多
目的:建立了一种灵敏、快速的高效液相色谱-串联质谱法测定动物源性食品中喹赛多残留量。方法:样品用酸性乙腈-甲醇混合溶剂提取,经正己烷除脂,HLB 固相萃取小柱净化后,以水-乙腈-甲酸(70:30:0.1)为流动相,采用 YMC-Pack Pro C_(18)柱分...目的:建立了一种灵敏、快速的高效液相色谱-串联质谱法测定动物源性食品中喹赛多残留量。方法:样品用酸性乙腈-甲醇混合溶剂提取,经正己烷除脂,HLB 固相萃取小柱净化后,以水-乙腈-甲酸(70:30:0.1)为流动相,采用 YMC-Pack Pro C_(18)柱分离,用电喷雾正离子源进行离子化,多反应监测方式(MRM)对喹赛多的母离子(m/z 272)及其子离子(m/z188和143)进行检测。结果:本方法研究的喹赛多的线性范围为0～50 ng·mL^(-1),线性相关系数 r 大于0.9980;在10～40μg·kg^(-1)的3个添加水平范围内的平均回收率为69.10%～93.54%;相对标准偏差为2.49%～9.03%;方法检出限(LOD)为3μg·kg^(-1)。结论:该方法灵敏、准确、分析速度快,适用于喹赛多残留量检测和确证以及动力学的研究。展开更多
基金supported by the National Basic Research Program of China (2009CB118805)the Key Technologies R&D Program of China during the 11th-Five Year Plan period (2009BADB7B05-03)
文摘Pharmacokinetics of cyadox （CYX） and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox （BDCYX）, cyadox-1-monoxide （CYX-1-O） and quinoxaline-2-carboxylic acid （QCA）, three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox （CYX） was administered to 8 healthy cross-bread swine intravenously （i.v.） and orally （p.o.） at a dosage of 1 mg kg^-1 body weight and 40 mg kg-1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve （AUC0-∞） were （0.38±0.03） lag mL-I h （CYX）, （0.018±0.002） lag mL-1 h （BDCYX） and （0.17±0.02） lag mL^-1 h （CYX- 1-O）, respectively. The terminal elimination half-lives （t1/2kz） were determined to be （0.93±0.07） h （CYX）, （1.45±0.04） h （BDCYX）, and （0.92±0.04） h （CYX-1-O）, respectively. Steady-state distribution volume （Vss） of （2.14±0.11） L kg^-1 and total body clearance （CL） of （2.84±0.19） L h^-1 kg^-1 were determined for CYX after i.v. dosing. The bioavailability （F） of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations （Cmax） of （1.08±0.06） lag mL^-1 （CYX）, （0.0068~ 0.0004） lag mL-1 （BDCYX） and （0.25~0.03） gg mL-~ （CYX-I-O） were observed at Tmax of 0.033 h （CYX）, 1 h （BDCYX） and 0.033 h （CYX-1-O）, respectively. The main pharmacokinetic parameters after p.o. administration were as follows： AUC0.= were （0.42~0.04） lag mL^-1 h （CYX）, （1.38±0.14） μg mL-1 h （BDCYX）, （0.59±0.02） lag mL-1 h （CYX-1-O） and （1.48＋0.09） lag mL-＇ h （QCA）, respectively, t1/2λz were （4.77±0.33） h （CYX）, （5.77±0.56） h （BDCYX）, （4.12＋0.28） h （CYX-1-O）, and （8.51＋0.39） h （QCA）, respectively. After p.o. administration, CmaxS of （0.033±0.002） μg mL^-1 （CYX）, （0.22±0.03） mg mL^-1 （BDCYX）, （0.089±0.005） μg mL^-1 （CYX-1-O）, and （0.17± 0.01） mg mL^-1 （QCA） were observed at Tmax of（7.38±0.33） h （CYX）, （7.25±0.31） h （BDCYX）, （7.38±0.33） h （CYX-1-O）, and （7.25±0.31） h （QCA）, respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve （AUC0-∞）of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives （t1/2λz） of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.
文摘150只去势长大仔猪随机分为6组,Ⅰ和Ⅳ组饲喂不含抗菌药的基础日粮,Ⅱ和Ⅴ组基础日粮中添加喹乙醇100m g/kg,Ⅲ和Ⅵ组基础日粮中添加喹赛多100 m g/kg。Ⅳ、Ⅴ和Ⅵ组仔猪灌服1010CFU产肠毒素性大肠杆菌(O139∶K88),Ⅰ、Ⅱ和Ⅲ组仅灌服肉汤。结果表明,喹赛多饲喂猪直肠粪便中大肠杆菌总数和接种的血清型大肠杆菌数与喹乙醇饲喂猪均无显著差异(P>0.05),喹赛多和喹乙醇饲喂猪直肠粪便中接种的血清型大肠杆菌数均低于非药物饲喂猪(P<0.05)。Ⅳ组仔猪感染率为68%;Ⅴ和Ⅵ组感染率均为16%。药物饲喂猪平均日增重显著改善(P<0.05),喹赛多饲喂猪平均日增重高于喹乙醇饲喂猪(P<0.05)。Ⅳ组仔猪平均日增重和饲料转化率分别下降9.6%和8.4%,Ⅵ组仔猪日增重和饲料转化率分别提高11.9%和7.9%,均高于Ⅴ组(4.2%和1.5%)。可见喹赛多不仅对断奶仔猪产肠毒素大肠杆菌感染有显著预防作用,而且还有较好的促进生长和提高饲料转化率作用。
文摘目的:建立了一种灵敏、快速的高效液相色谱-串联质谱法测定动物源性食品中喹赛多残留量。方法:样品用酸性乙腈-甲醇混合溶剂提取,经正己烷除脂,HLB 固相萃取小柱净化后,以水-乙腈-甲酸(70:30:0.1)为流动相,采用 YMC-Pack Pro C_(18)柱分离,用电喷雾正离子源进行离子化,多反应监测方式(MRM)对喹赛多的母离子(m/z 272)及其子离子(m/z188和143)进行检测。结果:本方法研究的喹赛多的线性范围为0～50 ng·mL^(-1),线性相关系数 r 大于0.9980;在10～40μg·kg^(-1)的3个添加水平范围内的平均回收率为69.10%～93.54%;相对标准偏差为2.49%～9.03%;方法检出限(LOD)为3μg·kg^(-1)。结论:该方法灵敏、准确、分析速度快,适用于喹赛多残留量检测和确证以及动力学的研究。
