辛鹅温敏原位凝胶经鼻给药后木兰脂素血浆含量的测定及药动学研究  

Study on content determination and pharmacokinetics of magnolin in rat plasmafrom Xinyi(Magnoliae Flos)-Ebushicao(Centipedae Herba) thermosensitive in situ gels after intranasal administration

作　　者：颜红[1] 彭志荣 高司琪 骆慧婷 欧阳威 YAN Hong;PENG Zhirong;GAO Siqi;LUO Huiting;OUYANG Wei(School of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208

出　　处：《湖南中医药大学学报》2022年第4期571-575,共5页Journal of Hunan University of Chinese Medicine

基　　金：湖南省中医药科研计划项目(2021223);长沙市自然科学基金项目(Kq2007066);湖南中医药大学一流学科项目(201803);中药学一级学科开放基金项目(2020ZYX09);中药学一级学科开放基金项目(2020ZYX13)。

摘　　要：目的建立辛鹅温敏原位凝胶经鼻给药后大鼠血浆中木兰脂素的液相色谱-串联质谱(liquid chromatography mass spectrometry/mass spectrometry,LC-MS/MS)检测方法,并探讨其在大鼠体内的药动学特性。方法大鼠滴鼻给予辛鹅鼻用温敏原位凝胶(1.5 mL/kg)后于不同时间点腹主动脉取血,应用梯度洗脱程序进行色谱分离,用LC-MS/MS技术检测,以采样时间对血药浓度建立药-时曲线,采用DPS 15.10软件计算药动学参数。结果在2~500 ng/mL范围内,木兰脂素与内标的峰面积比值与浓度的线性关系良好。大鼠滴鼻给予辛鹅鼻用温敏原位凝胶,其主要药动学参数分别为达峰时间T_(max)为(0.46±0.03)h,达峰浓度C_(max)为(230.83±55.17)ng/mL,半衰期T_(1/2)为(2.98±0.43)h,体内平均驻留时间MRT为(4.30±0.62)h,药-时曲线下面积值AUC_(0-24)为(1035.34±200.65)ng·h/mL、AUC_(0-∞)为(1089.22±201.00)ng·h/mL,总清除率CL为(1278.30±226.46)L/(kg·h)。结论建立的LC-MS/MS检测方法灵敏度高、专属性强,适用于大鼠体内的木兰脂素药动学研究。辛鹅温敏原位凝胶经鼻给药后,木兰脂素在大鼠体内的过程符合一室模型。Objective To establish a liquid chromatography mass spectrometry/mass spectrometry (LC -MS/MS) method for determination of magnolin and study its pharmacokinetics after intranasal delivery of Xinyi (Magnoliae Flos) -Ebushicao(Centipedae Herba) thermosensitive in situ gels.Methods Blood samples were taken from abdominal aorta at different time points after intranasal delivery of Xinyi (Magnoliae Flos) -Ebushicao (Centipedae Herba) thermosensitive in situ gels in rats (1.5 mL/kg).The gradient elution program was used for chromatographic separation.The LC-MS/MS was applicated for detection.The plasma drug concentration-time curve was established by the sampling time to blood drug concentration.The pharmacokinetic parameters were obtained calculated with DPS 15.10 software.Results There was a good linear relationship between peak area ratio and concentration of magnolin and internal standard within range of 2~500 ng/mL.After intranasal administration of Xinyi (Magnoliae Flos)-Ebushicao (Centipedae Herba) thermosensitive in situ gels in rats,the main pharmacokinetics parameters were as follows:the peak time T_(max)was (0.46±0.03) h,the peak concentration C_(max)was (230.83±55.17) ng/mL,the half-life T_(1/2)was (2.98±0.43) h,the average residence time MRT was (4.30±0.62) h,the area under the drug-time curve AUC_(0-24)was (1035.34±200.65) ng·h/mL,AUC_(0-∞)was (1089.22±201.00) ng·h/mL,and the total clearance CL was (1278.30±226.46) L/(kg·h).Conclusion The established LC-MS/MS method has the high sensitivity and strong specificity,and it can be used for the pharmacokinetic study of magnolin in rats.The process of magnolin in rats conforms to one-compartment model after intranasal delivery of Xinyi (Magnoliae Flos)-Ebushicao (Centipedae Herba) thermosensitive in situ gels.

关 键 词：原位凝胶 辛夷 鹅不食草 木兰脂素 药动学 液相色谱-串联质谱 血药浓度 

分 类 号：R285.5[医药卫生—中药学]