泰地罗新注射液在猪体内的药代动力学研究

发布时间：2018-02-09 03:23

  本文关键词： 泰地罗新 液质联用 药代动力学　出处：《吉林大学》2015年硕士论文　论文类型：学位论文

【摘要】：泰地罗新(Tildipirosin,TIP)是一种新型的大环内酯类半合成抗菌药,是泰乐菌素的衍生物。泰地罗新是一种广谱、高效的抗微生物药,对引起猪呼吸道疾病的病原菌,如胸膜肺炎放线杆菌、多杀性巴氏杆菌、支气管败血波氏杆菌、副猪嗜血杆菌等,以及引起牛呼吸道疾病的病原菌,如溶血性曼海姆菌、多杀性巴氏杆菌、睡眠嗜组织菌等具有特效,是治疗呼吸道疾病极为理想的药物。目前,在我国还未上市,属于正在研究中的新兽药。本研究建立了以泰乐菌素为内标的液质联用检测方法,并完成了泰地罗新注射液在猪体内的药代动力学研究。检测方法的质谱条件:采用电喷雾离子源(ESI)正离子模式,检测方式为多反应监测(MRM)扫描模式,喷雾电压:5.5 k V,离子源温度(TEM):600℃,气帘气(CUR)压力:20 psi,雾化气(GS1)压力:35 psi,辅助加热气(GS2)压力:40 psi,碰撞气(CAD)压力:9 psi。泰地罗新和泰乐菌素用于定量的离子分别为:m/z→735.1/98.0和m/z→917.6/174.4。色谱条件:色谱柱为SB-C18(2.1mm×150 mm,3.5μm)色谱柱,以乙腈-0.1%甲酸水溶液(v/v=1:9)为流动相,按0 min(10:90),1 min(10:90),6 min(60:40),6.4 min(95:5),12 min(95:5),12.1 min(10:90),18 min(10:90)进行梯度洗脱,流速0.25 m L/min,柱温为20℃,进样量10.0μL。样品用乙腈提取,氮气吹干,流动相溶解制备待检样品。泰地罗新在0.005-0.8μg/m L的浓度范围内呈现良好的线性关系,相关系数为0.9994,检测限为0.002μg/m L,定量限为0.005μg/m L,该方法的平均回收率在86.96%-95.52%,日内和日间变异系数均小于15%。且泰地罗新在室温、-80℃长期冷冻及反复冻融条件下的稳定性均良好,符合生物样品的分析要求。该实验方法灵敏度高,操作简便,可以用于泰地罗新在猪体内的药代动力学研究。药代动力学结果:通过给猪肌肉注射2、4和8 mg/kg bw三个不同剂量组,用DAS 3.0(Bio Guider Co.,Shanghai,China)软件非房室模型对数据进行分析。其主要的药代动力学参数如下:达峰时间Tmax分别为0.208±0.165、0.389±0.18、0.236±0.153 h,峰浓度Cmax分别为0.475±0.114、0.972±0.391、0.987±0.164μg/m L,半衰期t1/2分别为118.69±33.78、124.45±42.06、82.73±23.69 h,药时曲线下面积AUC分别为11.04±1.27、15.75±5.19、37.54±4.83μg/m L*h。以上实验数据为泰地罗新注射液在临床合理用药提供了理论依据。
[Abstract]:TildipirosinTIP) is a new type of macrolide semi-synthetic antimicrobial agent, which is a derivative of tylosin. It is a broad-spectrum, highly effective antimicrobial agent against pathogens causing respiratory diseases in pigs, such as Actinobacillus pleuropneumoniae. Pasteurella multocida, Pasteurella bronchus, Haemophilus parais, and other pathogens that cause bovine respiratory diseases, such as Mannheim haemolyticus, Pasteurella multocida, histiophilic sleep bacteria, etc., have special effects. It is an ideal drug for the treatment of respiratory tract diseases. At present, it is a new veterinary drug under study, which is not yet on the market in China. In this study, a liquid-mass spectrometry method with tylosin as the internal standard was established. The pharmacokinetics of tadirosin injection in pigs was studied. The mass spectrometry conditions were as follows: electrospray ion source (ESI) positive ion mode and multi-reaction monitoring (MRM) scanning mode. Spray voltage: 5.5 kV, ion source temperature Tem: 600 鈩，

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