阿苯达唑亚砜盐酸盐有关物质的HPLC检测

为了建立阿苯达唑亚砜盐酸盐中有关物质的检测方法,本文采用高效液相色谱(HPLC)方法,通过系统适用性、专属性、检测限等试验,确定了阿苯达唑亚砜盐酸盐中有关物质的HPLC检测方法。色谱条件:采用C18色谱柱,流动相为乙腈-蒸馏水(40∶60),检测波长为230nm。结果显示:阿苯达唑亚砜盐酸盐在1.25～40.0μg/mL浓度范围内线性关系良好,检测限为0.032μg/mL。在此条件下阿苯达唑亚砜盐酸盐与其合成原料阿苯达唑、合成中可能产生的阿苯达唑砜、降解产物分离情况良好。     

高效液相色谱法测定动物肌肉中的阿苯达唑及其代谢物

建立了动物肌肉组织中阿苯达唑及其代谢物阿苯达唑亚砜、阿苯达唑砜的多残留检测的高效液相色谱法。用乙酸乙酯提取肌肉组织样品中的药物,提取液浓缩后加入酸性乙醇和正己烷分配脱脂,过watersHLB固相萃取柱净化。以水-乙腈-甲酸为流动相,反相高效液相色谱紫外检测法检测。方法的平均回收率为86．4％,平均变异系数为1．96％。3种药物的检测限均为5μg／kg,定量限均为20μg／kg。     

盐酸阿苯达唑亚砜的合成

以阿苯达唑为原料,采用一锅合成法,通过氧化、酸化反应得到目标产物盐酸阿苯达唑亚砜。以丙酮为反应溶剂,当阿苯达唑和盐酸的投料比为30 g∶13 mL,阿苯达唑和双氧水的投料比为1∶1.01(n∶n),反应时间为30 min时,制备的盐酸阿苯达唑亚砜的收率为95.78%,通过IR、1H-NMR1、3C-NMR和ESI-MS分析对其产物结构进行了确证。     

盐酸阿苯达哩亚砜化学结构分析

建立了药物盐酸阿苯达唑亚砜的化学结构确证方法.通过高效液相色谱(HPLC)测定盐酸阿苯达唑亚砜纯度,采用紫外光谱(UV)、红外光谱(IR)、核磁共振(NMR)以及质谱(MS)等分析方法对盐酸阿苯达唑亚砜样品进行了结构测定.结果确证盐酸阿苯达唑亚砜的结构为[5-(丙亚砜基)-1H-苯并咪唑-2-基]氨基甲酸甲醋盐酸.本方法测定结果准确全面,为盐酸阿苯达唑亚砜的生产和鉴定提供了较为全面的参考数据.     

盐酸阿苯达哩亚砜化学结构分析

建立了药物盐酸阿苯达唑亚砜的化学结构确证方法.通过高效液相色谱(HPLC)测定盐酸阿苯达唑亚砜纯度,采用紫外光谱(UV)、红外光谱(IR)、核磁共振(NMR)以及质谱(MS)等分析方法对盐酸阿苯达唑亚砜样品进行了结构测定.结果确证盐酸阿苯达唑亚砜的结构为[5-(丙亚砜基)-1H-苯并咪唑-2-基]氨基甲酸甲醋盐酸.本方...     

盐酸阿苯达唑亚砜对照品候选物纯度检测方法的建立

以盐酸阿苯达唑亚砜原料为基础,通过反复提纯,得到盐酸阿苯达唑亚砜对照品候选物,该候选物经过熔点,薄层色谱法（TLC）和高效液相色谱法检测,初步确认符合对照品的要求,经过高效液相色谱检测,采用面积归一化法计算其纯度不小于99.5%。该方法的建立为盐酸阿苯达唑对照品进一步研究提供了帮助。     

联合应用阿苯达唑和伊维菌素在线虫感染鄂尔多斯细毛羊体内的药动学研究

为阐明联合应用阿苯达唑(ABZ)和伊维菌素(IVM)在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学互作关系,以感染胃肠道线虫的鄂尔多斯细毛羊为研究对象,比较研究了单独或联合应用阿苯达唑和伊维菌素后的药物动力学特征。通过粪便虫卵检查法,选取感染胃肠道线虫的鄂尔多斯细毛羊15只,随机分成3组,每组5只。第1组口服给予阿苯达唑(15mg/kg),第2组皮下注射伊维菌素(0.2mg/kg),第3组皮下注射伊维菌素(0.2mg/kg)的同时口服阿苯达唑(15mg/kg)。于给药后不同时间,由颈静脉采集血样,分离血浆,并用高效液相色谱法测定各时间点血浆阿苯达唑、阿苯达唑亚砜、阿苯达唑砜和伊维菌素浓度,并用PK Solution 2.0药物动力学软件计算出各药动学参数。结果表明,联合用药组绵羊血浆伊维菌素峰浓度(Cmax)、药时曲线下面积(AUC)和平均滞留时间(MRT)分别为44.80ng/mL±6.12ng/mL、5 007.46ng.h/mL±1 301.42ng.h/mL和85.47h±5.03h,均显著(P<0.05)小于单独用药组的对应参数值67.62ng/mL±9.06ng/mL、7 125.08ng.h/mL±908.52ng.h/mL和113.39h±9.00h。口服阿苯达唑组绵羊血浆中仅检测到了阿苯达唑砜和阿苯达唑亚砜,而未检测到阿苯达唑母药。联合用药后,除阿苯达唑砜的达峰时间(T max)显著推迟外,阿苯达唑砜和阿苯达唑亚砜的其他各参数之间均无显著性差异。因此,联合应用IVM和ABZ可影响它们在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学特征,且对伊维菌素药动学特征的影响尤为明显,在临床联合用药过程中应予以重视。     

超高效液相色谱-串联质谱法结合固相萃取净化测定牛奶中阿苯达唑及其主要代谢物残留量

本研究基于超高效液相色谱-串联质谱(UPLC-MS/MS)结合固相萃取净化技术,建立了阿苯达唑(ABZ)、阿苯达唑砜(ABZSN)、阿苯达唑亚砜(ABZSX)的定量分析方法,用以监控牛奶及其制品的质量安全.牛奶样品经过1％乙酸乙腈溶液提取后,提取液经氮气吹干,用碳酸盐缓冲溶液溶解后,使用C18固相萃取柱净化.将净化液注...     

绵羊血浆中三氯苯达唑及其代谢产物的HPLC同步测定方法的建立

为建立血浆样品中三氯苯达唑(TCBZ)及其代谢产物三氯苯达唑砜(TCBZSO2)和三氯苯达唑亚砜(TCBZSO)的高效液相色谱同步检测方法,以甲苯咪唑(MBZ)为内标物,将加有目标物标准品的新鲜绵羊血浆样品经甲醇提取净化和氮气浓缩等前处理后,供HPLC检测;并对以上3种目标物紫外检测方法的专属性、稳定性、准确度和灵敏度等进行了系统研究。结果表明,三氯苯达唑、三氯苯达唑砜、三氯苯达唑亚砜以及内标物甲苯咪唑的保留时间分别为10.021、4.373、5.407、3.420min,分离良好,且不受干扰峰的影响;目标物均在0.05μg/mL～6.4μg/mL范围内呈现良好的线性关系,R2分别为0.999 5、0.999 0和0.999 1;血浆样品被测物含量的日内和日间变异系数(CV)分别小于1%和12%;绝对回收率分别为84.96%、83.84%和86.27%,内标物甲苯咪唑的绝对回收率为90.16%;最低检测限为0.05μg/mL。表明该方法适用于跟踪检测三氯苯达唑及其代谢产物在绵羊血浆中的浓度,是一种稳定而准确的检测方法。     

五氯柳胺阿苯达唑复方混悬液的制备及其含量测定

为制备五氯柳胺阿苯达唑复方混悬液,对其质量评价并建立含量测定方法。通过辅料相容性、单因素筛选及回归正交设计,以沉降体积比、再分散性等为考察因素,优化处方制备五氯柳胺阿苯达唑复方混悬液,用激光粒度测定仪、透射电子显微镜,对其粒径和形态进行测定,考察制剂的稳定性,建立测定五氯柳胺阿苯达唑复方混悬液含量的高效液相色谱方法。结果显示,五氯柳胺阿苯达唑复方混悬液每100 mL中含五氯柳胺4.00 g,阿苯达唑4.00 g,黄蓍树胶0.25 g,十二烷基硫酸钠0.20 g,甘油3.00 mL,柠檬酸钠1.20 g,苯甲酸0.15 g。混悬液沉降体积比为0.99,再分散性良好。1～100 mg/L的五氯柳胺、阿苯达唑与峰面积呈良好的线性关系(R~2=0.999 9,R~2=0.999 7),平均回收率为101.15%和100.89%,RSD为0.13%和0.10%(n=9)。结果表明,制备的五氯柳胺阿苯达唑复方混悬液工艺简单,性状良好,稳定性和分散性好,质量可控。所建立的高效液相色谱法快速简便、准确可靠,可用于复方混悬液中五氯柳胺、阿苯达唑含量的测定。     

Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200 000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13–18 groups ( n = 5–10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6–1.4, 4.7–9.0, 4.5–18.9, 1.8–3.1, 0.9–3.0, 3.4–9.6, 5.0–16.1 and 7.4–12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 μg/g in various tissues ranged from 5.0–11.6. 70.0–110.5. 114.0–179.8, 21.3–30.3,4.1–24.8 and 47.8–84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals.     

牛奶中苯并咪唑类药物及其代谢物残留的UPLC-MS/MS检测方法研究

建立了牛奶中苯并咪唑类药物及代谢物残留的UPLC-MS/MS检测方法。牛奶样品在弱碱性条件下经乙腈沉淀蛋白后,用乙酸乙酯提取,再经正己烷脱脂,MCX固相萃取柱净化,采用UPLC-MS/MS多反应监测(MRM)模式检测,外标法定量。本方法对苯并咪唑类药物及代谢物的检测限均为5μg/g,定量限均为10μg/g,在10～200μg/L添加浓度范围内回收率为69.9%～113.1%之间,批内变异系数在1.36%～11.48%之间,批间变异系数在1.09%～9.87%之间。本方法分析速度快,灵敏度高,重现性好,各项技术指标均满足国内外相关法规要求,可用于牛奶中苯并咪唑类药物及代谢物残留的检测。     

高效液相色谱法检测羊鸡组织中氟苯达唑、噻苯达唑及其代谢物残留量的研究

建立了一种可同时检测羊组织（肌肉、肝脏、肾脏、脂肪）、鸡组织（肌肉、肝脏）中氟苯达唑及代谢物2-氨基氟苯达唑、噻苯达唑及代谢物5-羟基噻苯达唑药物残留的高效液相色谱检测方法。结果表明：氟苯达唑及代谢物2-氨基氟苯达唑、噻苯达唑及代谢物5-羟基噻苯达唑在0.02～1.5μg/mL浓度范围内呈良好的线性关系r,均大于0.999。方法的定量限为20μg/kg。在鸡组织（肌肉、肝脏）中,两种药物及其代谢物在20～800μg/kg的添加浓度范围内,其回收率范围在60%～100%之间;在羊组织（肌肉、肝脏、肾脏、脂肪）中,两种药物及其代谢物在20～200μg/kg的添加浓度范围内,其回收率范围在60%～100%之间;批内变异系数均小于15%、批间变异系数均小于20%。     

不同剂量阿苯达唑治疗鼠旋毛虫病效果初探

使用不同剂量阿苯达唑对人工感染旋毛虫的小白鼠进行疗效试验,观察其不同剂量的杀虫效果.结果表明：应用阿苯达唑20 mg/（kg·d）×7治疗鼠旋毛虫病有很好的治疗效果,为阿苯达唑临床应用提供科学参考.     

羊组织中三氯苯唑及代谢物残留量检测方法研究

建立了一种可同时检测羊组织中三氯苯达唑及其代谢物三氯苯达唑酮残留的高效液相色谱检测方法。结果表明三氯苯达唑、三氯苯达唑酮浓度在20～600 ng/mL范围时与峰面积呈良好的线性关系,R2均大于0.999 9,方法的定量限为30μg/kg。三氯苯达唑、三氯苯达唑酮在30～300μg/kg的浓度添加水平上,其回收率在60%～100%,批内、批间的相对标准偏差均小于15%。     

Effect of the ionophore antibiotic monensin on the ruminal biotransformation of benzimidazole anthelmintics

The benzimidazole (BZD) anthelmintics, netobimin (NTB) pro-drug and albendazole sulphoxide (ABZSO) are reduced to albendazole (ABZ) by ruminal microflora. The aim of the current work was to evaluate the influence of the ionophore monensin (MON) on the in vitro biotransformation of NTB and ABZSO by sheep ruminal fluid. Ruminal fluid, collected from Corriedale sheep, was preincubated (24 h) either without (control) or with known MON concentrations (0.5, 1.5 and 3.0 microg/mL) at 38 degrees C under a CO2 atmosphere. Afterwards, aliquots from both MON-pretreated and control ruminal fluid samples were incubated (30 and 60 min) with 2 microg/mL of either NTB or ABZSO. Incubated samples were chemically extracted and analysed by High Performance Liquid Chromatography to quantify the metabolites formed. The rate of ABZ production after 30 min of NTB incubation with control ruminal fluid was 0.023 microg/min. Conversely, the rates of ABZ formation were significantly (P<0.05) lower (0.009, 0.011 and 0.013 microg/min) when NTB was incubated with ruminal fluid pretreated with MON (at 0.5, 1.5 and 3.0 microg/mL, respectively). After both incubation periods, the reduction of ABZSO to ABZ was 22 to 70% lower when the ruminal fluid was preincubated with the different MON concentrations. The lower ABZ production observed in the presence of MON may result in a modified availability of this molecule in the gastrointestinal (GI) tract and hence, on its anthelmintic efficacy against GI nematodes.     

超高效液相色谱-串联质谱法测定水产品中群勃龙残留方法研究

建立了牛奶中苯并咪唑类药物及代谢物残留的超高效液相色谱-串联质谱检测方法。水产样品经乙酸乙酯提取,C18固相萃取柱净化,采用超高效液相色谱-串联质谱多反应监测模式检测,外标法定量。不同基质中,群勃龙在2-100 ng/mL的浓度范围内呈现良好的线性相关,相关系数为0.994以上;本方法对群勃龙群勃龙在鱼、虾、鳖、蟹类产品中的检测限为0.5μg/kg,定量限为1μg/kg;在贝类产品中的检测限为1μg/kg,定量限2μg/kg;不同水产品的基质中添加1-10μg/kg浓度范围内,其回收率为74.2%-119%,批内变异系数在1.0%-9.0%之间,批间变异系数在0.3%-8.5%之间。本方法分析速度快,灵敏度高,重现性好,各项技术指标均满足国内外相关法规要求,可用于水产品中群勃龙的残留检测。     

乙酰甲喹及其主要代谢物在鸡体内的残留消除规律研究

建立了高效液相色谱串联质谱（HPLC—MS／MS）法用于乙酰甲喹及其6种主要代谢物的检测。将65只健康白羽鸡分为两组,10只为空白对照组,其余为试验组。试验组施以20mg／kgb．w．灌胃乙酰甲喹悬浊液,1d2次,连续3d。在给药结束后2、4、6、12、16、24、30、36、48、72、120h分别宰杀5只鸡,采集血液和可食性组织（肌肉、肝脏、肾脏和皮脂）样品。结果表明：乙酰甲喹原药在组织和血浆中迅速消除;乙酰甲喹的代谢物广泛存在于鸡的可食性组织和血浆中;代谢物的残留消除过程较为复杂,代谢物在肌肉和肝脏中残留量较多,在皮脂中残留时间最长。研究结果将有助干榍示7．酷甲喹存鸡体内的砖留消除期,律．     

不同用药方法对牦牛多头蚴病的疗效试验

[目的]观察三种不同用药方法对高原型牦牛多头蚴病的治疗效果。[方法]采用吡喹酮增量法、阿苯达唑增量法、吡喹酮和阿苯达唑联合法治疗牦牛多头蚴病。[结果]吡喹酮增量法试验组,症状消失的平均时间为8.25 d;有效率为80.9%,治愈率为72.7%;阿苯达唑增量法试验组,症状消失的平均时间为10.6 d,有效率为100%,治愈率为90.9%;吡喹酮与阿苯达唑联合法组,症状消失的平均时间为12.43 d,有效率为80%,治愈率为60%。[结论]吡喹酮增量法疗效较其它组快;阿苯达唑增量法效果缓慢,但疗效较高;联合用药法疗效欠佳。     

Albendazole repeated administration induces cytochromes P4501A and accelerates albendazole deactivation in mouflon (Ovis musimon)

Adult mouflon ewes (Ovis musimon) were treated repeatedly with therapeutic doses of albendazole (ABZ, p.o. 7.5 mg/kg of body weight/day, for five consecutive days). Animals (treated or control) were sacrificed 24 h after the fifth dose of ABZ and liver and small intestine were collected to prepare microsomes. The activities of several biotransformation enzymes were measured in both hepatic and intestinal microsomes. A significant increase in the activity and amount of cytochromes P4501A (CYP1A) was observed in both tissues of ABZ treated mouflons compared to control animals. No other biotransformation enzymes tested were affected by five ABZ doses. The in vitro biotransformation of ABZ was studied in hepatic and intestinal microsomes from ABZ treated and control mouflons. Concentrations of two main ABZ metabolites - pharmacologically active ABZ sulfoxide and pharmacologically inactive ABZ sulfone were analysed using HPLC. A significant increase in rate of formation of ABZ sulfone (which is catalysed by CYP1A) was observed in hepatic as well as in intestinal microsomes from ABZ treated animals. The enhancement of ABZ deactivation by its repeated administration may affect the anthelmintic efficacy of this drug and may contribute to the development of parasite resistance.