Simultaneous Determination of Fucoxanthin and Its Deacetylated Metabolite Fucoxanthinol in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry

Fucoxanthin and its deacetylated metabolite fucoxanthinol are two major carotenoids that have been confirmed to possess various pharmacological properties. In the present study, fucoxanthinol was identified as the deacetylated metabolite of fucoxanthin, after intravenous (i.v.) and intragastric gavage (i.g.) administration to rats at doses of 2 and 65 mg/kg, respectively, by liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. Next, an accurate and precise LC-MS/MS method was developed to quantitatively determine fucoxanthin and fucoxanthinol in rat plasma. Plasma samples were resolved by LC-MS/MS on a reverse-phase SB-C18 column that was equilibrated and eluted with acetonitrile (A)/aqueous 0.1% formic acid (B; 92/8, v/v) at a flow rate of 0.5 mL/min. Analytes were monitored by multiple-reaction monitoring (MRM) under positive electrospray ionization mode. The precursor/product transitions (m/z) were 659.3→109.0 for fucoxanthin, 617.2→109.0 for fucoxanthinol, and 429.4→313.2 for the internal standard (IS). Calibration curves for fucoxanthin and fucoxanthinol were linear over concentrations ranging from 1.53 to 720 and 1.17 to 600 ng/mL, respectively. The inter- and intraday accuracy and precision were within ±15%. The method was applied successfully in a pharmacokinetic study and the resulting oral fucoxanthin bioavailability calculated.     

蚕病灵的药物动力学试验

试验采用微生物法,测定了家蚕食下蚕药“蚕病灵”后血液中的药物含量随时间变化的规律,经试验确定血清药物浓度-时间曲线符合一级吸收动力学和单室模型特征,其关系式为:C=9.768(e-0.145t-e-0.848t);实测血药浓度-时间曲线与理论血药浓度-时间曲线的相关系数r=0.9142,并求出了“蚕病灵”一系列药物动力学参数。     

乙酰甲喹在美洲鳗鲡体内的药物代谢动力学及残留研究

在水温(25±1)℃条件下,分别采用口灌和浸浴的给药方式,以120mg·kg~(-1)的单剂量混饲口灌及5mg·L~(-1)浸浴18h给予乙酰甲喹后,用高效液相色谱法测定血浆、肌肉、肝脏及肾脏中的药物浓度,研究不同给药方式下乙酰甲喹在美洲鳗鲡体内的药代动力学特征及残留情况。结果表明:乙酰甲喹原药在美洲鳗鲡体内吸收良好、代谢快、体内残留少。口灌给药后,血浆中药物浓度达峰时间T_(max)为0.75h,达峰质量浓度C_(max)为4 115μg·L~(-1),消除相半衰期T_(1/2)为7.40h,总体消除率CL/F为41.89L·kg~(-1)·h~(-1),72h后血浆、肌肉、肝脏及肾脏中几乎检测不到原药;浸浴给药血浆中药物浓度于0.25h达峰,达峰质量浓度C_(max)为435.6μg·L~(-1),消除相半衰期T_(1/2)为0.26h,总体消除率CL/F为1.241L·kg~(-1)·h~(-1),2.5h后各组织中几乎检测不到原药。2种方式给药乙酰甲喹在美洲鳗鲡血浆中分布均符合药动学一室开放模型。     

枳壳对丁螺环酮在健康大鼠体内药物动力学的影响

目的 研究枳壳对丁螺环酮在健康大鼠体内药物动力学的影响。方法 将SD大鼠随机分为丁螺环酮组,丁螺环酮加枳壳低剂量组（15 g/kg）,丁螺环酮加枳壳高剂量组（30 g/kg）,测定给药后5、10、20、30、45、60、90、120、240、360、480、600 min丁螺环酮的血药浓度,计算并比较其药动学参数。结果 与丁螺环酮组比较,丁螺环酮加枳壳低剂量组和高剂量组中丁螺环酮AUC_（0-t）分别增加2.49和4.18倍,C_max分别增加1.63和2.57倍,T_max从0.28 h分别延长至0.52和1.06 h,t_1/2从0.96 h分别延长至2.18和4.87 h,差异具有统计学意义（P<0.05）。结论 枳壳可增加同服药物丁螺环酮的AUC_（0-t）和C_max,提高丁螺环酮生物利用度,并有剂量依赖性趋势,枳壳与丁螺环酮发生显著的药动学相互作用。     

Pharmacokinetics of Eugenol in Japanese Flounder,Paralichthys olivaceus

Eugenol, which has been used as an anesthetic for fish, was administered to Japanese flounder, Paralichthys olivaceus (127 ± 50.8 g), by bath treatment at concentrations of 0.025, 0.125, and 0.25 mL/L seawater for 10 min and intramuscular injection at 40 μL/fish to investigate the pharmacokinetic characteristics of eugenol in the plasma of Japanese flounder. In the bath treatment test, plasma eugenol concentration increased with increasing eugenol concentration up to 0.125 mL/L and reached steady state within 5 min. After a 10‐min bath treatment in 0.25 mL/L eugenol, plasma eugenol concentration was about 58.4 µg/mL. After transfer into running seawater, plasma eugenol concentration decreased biphasically with half‐lives of 0.0296 h (α‐phase) and 0.289 h (β‐phase). The AUC_0000→0800 was about 16.5 µg h/mL. In administration by intramuscular injection, plasma eugenol concentration increased rapidly after administration and decreased biphasically with half‐lives of 0.0329 h (α‐phase) and 8.08 h (β‐phase). The AUC_0000→0800 was about 52.5 µg h/mL. In both methods of administration, Japanese flounder with average weight of 127 g were effectively anesthetized when plasma eugenol concentrations were between 2.19 and 4.88 µg/mL.     

多拉菌素浇泼剂在犬体内的药代动力学

本试验对多拉菌素浇泼剂在犬血浆中的药代动力学进行了研究。犬背部皮肤一次浇注多拉菌素浇泼剂(0.1 mg/kg体重),给药后,不同时间点从犬前肢静脉采血。以高效液相色谱法对血浆中药物浓度进行测定,血浆药物浓度—时间数据用WinNonlin 5.2.1的非房室模型药动软件处理。给药后的主要药物动力学参数为:t1/2β为(2.14±0.56)d,T_max为(1.00±0.00) d,C_max为(24.38±4.82) ng/mL,AUC为(89.79±16.90)ng/(d·mL)。提示多拉菌素浇泼剂在犬体内血药浓度维持的时间较长,消除缓慢。     

喹烯酮及其主要代谢物在猪体内的药动学研究

本试验旨在研究喹烯酮及其主要代谢物在猪体内的药物代谢动力学过程。将喹烯酮按40 mg/kg的剂量对7头猪进行灌胃给药,采用HPLC-MS/MS法测定血浆中喹烯酮及其主要代谢物的浓度,药代动力学软件WinNonlin 5.2处理血浆中药物浓度－时间数据。灌胃给药后猪血浆中能检测到原药和N1-脱氧喹烯酮、脱二氧喹烯酮及3-甲基喹噁啉-2-羧酸(MQCA)3种代谢物。喹烯酮的浓度－时间数据符合一级吸收一室开放模型,其主要药代动力学参数为:T_1/2Ka＝(0.97±0.08)h,T_1/2λz＝(2.79±0.16)h,CL＝(26.03±0.65)L/h·kg,Cmax＝(0.26±0.01)μg/mL,Tmax＝(2.23±0.06)h,AUC＝(1.54±0.04)h·μg/mL;采用统计矩法处理N1-脱氧喹烯酮和脱二氧喹烯酮的浓度－时间数据,N1-脱氧喹烯酮主要药代动力学参数为:Tmax＝(6.33±1.37)h,Cmax＝(8.81±2.08) ng/mL,T_1/2λz＝(3.03±1.27)h,AUC＝(0.07±0.01)h·ng/mL,MRT＝(6.58±0.40)h;脱二氧喹烯酮的主要药动学参数:Tmax＝(10.29±0.29)h,Cmax＝(6.20±1.11)ng/mL,T_1/2λz＝(5.84±2.78)h,AUC＝(0.15±0.01)h·ng/mL,MRT＝(3.64±0.72)h。同时,在少数时间点检测到代谢物MQCA。猪口服喹烯酮后,吸收较快,消除较慢。血浆中检测到N1-脱氧喹烯酮、脱二氧喹烯酮及3-甲基喹噁啉-2-羧酸3种代谢物,且浓度较低、消除缓慢。     

甲砜霉素在鲫体内的药物代谢动力学研究

采用液相色谱串联质谱法,研究通过单剂量口灌给药,对甲砜霉素在鲫(Carassius auratus)体内的药代动力学进行研究,为甲砜霉素在鲫疾病预防和治疗方面提供理论基础。给药剂量为30 mg/kg体重,实验水温(20±0.2)℃,鲫平均体重(40.70±7.87)g。取给药后0.25、0.5、1、1.5、2、4、6、8、12、24、36、48、72 h鲫的肌肉、血浆、肝脏、肾脏,测定各组织中甲砜霉素的浓度,用药动学3p97软件进行数据的处理和分析。结果表明:甲砜霉素在鲫体内吸收分布迅速,符合一级吸收二室开放模型,但消除缓慢。甲砜霉素在鲫血浆、肝脏、肾脏和肌肉中的主要药代动力学参数如下:分布半衰期(T1/2α)分别为1.446 h、1.958 h、7.410 h和1.376 h;消除半衰期(T1/2β)分别为16.712 h、21.267 h、79.970 h和25.600 h;药时曲线下总面积(AUC)分别为669.073μg/(mL.h)、271.260μg/(g.h)、3616.060μg/(g.h)和158.634μg/(g.h)。甲砜霉素在水产动物体内吸收快,肌肉和肾脏消除半衰期长,消除缓慢,因此,在该类药物使用时,应相对延长给药间隔时间,避免耐药性的产生。     

乙酰甲喹在绵羊体内的药物动力学研究

【目的】分析乙酰甲喹(Mequindox)在成年绵羊体内的药物动力学过程,为兽医临床合理用药提供理论依据。【方法】绵羊单剂量快速静脉注射乙酰甲喹7 mg/kg,7 h内不同时间12次颈静脉采血,用高效液相色谱法测定血药浓度。【结果】乙酰甲喹在绵羊体内的药物动力学配置符合无吸收因素一室开放模型,其药-时曲线最佳方程为:C=10.833e-0.340 4t;主要药物动力学参数:半衰期(t(1/2))为(2.062 2±0.264 5)h,药-时曲线下面积(AUC)为(32.367 6±2.921 6)μg/mL.h,表观分布容积(Vd)为(0.642 7±0.042 9)L/kg,体清除率(CLB)为(0.217 7±0.019 3)L/(kg.h)。【结论】乙酰甲喹在绵羊体内分布广泛,消除较快。     

噬菌体药代动力学研究进展

抗生素在全球广泛使用,导致细菌耐药性问题日益严重,甚至产生MRSA这样的超级耐药菌,寻找新的抗生素替代药物成为目前医学治疗领域的重要趋势.噬菌体可以高效、特异地裂解细菌,与抗生素的作用机制完全不同,是新概念的抗菌物质,有着很大的研究与应用潜力.为了正确评价噬菌体在动物体内的疗效及安全性,必须研究其在机体内吸收、分布、代...