吸入用盐酸氨溴索溶液在大鼠肺组织内的药物代谢动力学研究
Pharmacokinetic Study of Ambroxol Hydrochloride Solution for Inhalation in Lung Tissue of Rats
平丽 1洪雅雯 1吴玥1
作者信息
- 1. 浙江大学药学院·浙江大学药物安全评价研究中心,浙江 杭州 310058
- 折叠
摘要
目的 考察吸入用盐酸氨溴索溶液在大鼠肺组织内的药物代谢动力学(简称药动学)特征.方法 采用超高效液相色谱串联质谱(UPLC-MS/MS)法测定SD大鼠肺组织中盐酸氨溴索含量,色谱柱为Waters Acquity UPLC BEH C18 柱(100 mm×2.1 mm,1.7µm),流动相为 0.1%甲酸水溶液-乙腈(梯度洗脱),流速为 0.3 mL/min,柱温为 35℃,进样量为 5µL;采用电喷雾离子源,正离子多反应监测模式.通过给予大鼠吸入用盐酸氨溴索溶液(相当于盐酸氨溴索 22.5 mg),分别于给药前及给药后 0.083,0.25,0.5,1,2,4,6,8,12,24 h采集大鼠肺组织,并以DAS 3.0 软件计算药动学参数.结果 大鼠肺组织内盐酸氨溴索质量浓度在 10～1 000 ng/mL范围内与待测成分与内标峰面积的比值线性关系良好(r=0.998 6,n=7);精密度、稳定性、回收试验及基质效应结果均符合方法学要求.半衰期(t1/2)为 4.33 h,峰浓度(Cmax)为 3 997.40 ng/g,药-时曲线下面积(AUC0-t)为 4 311.88(ng·h)/g,平均滞留时间(MRT0-t)为 2.74 h,清除率为 5.05(L·h)/kg.结论 该方法操作简便,结果准确可靠,可用于大鼠肺组织内吸入用盐酸氨溴索溶液的药动学研究.
Abstract
Objective To investigate the pharmacokinetic characteristics of Ambroxol Hydrochloride Solution for Inhalation in the lung tissue of rats.Methods Ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was used to determine the content of ambroxol hydrochloride in the lung tissue of SD rats.The chromatographic column was the Waters Acquity UPLC BEH C18 column(100 mm×2.1 mm,1.7 µm),the mobile phase was 0.1% formic acid aqueous solution-acetonitrile(gradient elution),the flow rate was 0.3 mL/min,the column temperature was 35℃,and the injection volume was 5 µL.The electron spray ionization was adopted with the positive-ion multiple reaction monitoring mode.The lung tissues of rats were collected before giving Ambroxol Hydrochloride Solution for Inhalation and after 0.083,0.25,0.5,1,2,4,6,8,12,24 h of giving this drug(equivalent to 22.5 mg ambroxol hydrochloride),and pharmacokinetic parameters were calculated by the DAS 3.0 software.Results The linear range of ambroxol hydrochloride in lung tissue of rats was 10-1 000 ng/mL(r=0.998 6,n=7).The results of precision,stability,recovery tests and matrix effect all met the methodological requirements.The half-life(t1/2)was 4.33 h,the peak concentration(Cmax)was 3 997.40 ng/g,the area under the plasma concentration-time curve(AUC0-t)was 4 311.88(ng·h)/g,the mean residence time(MRT0-t)was 2.74 h,and the clearance rate was 5.05(L·h)/kg.Conclusion This method is easy,accurate and reliable,which can be used for the pharmacokinetic study of Ambroxol Hydrochloride Solution for Inhalation in lung tissue of rats.
关键词
吸入用盐酸氨溴索溶液/大鼠/肺组织/药物代谢动力学/超高效液相色谱串联质谱法/含量测定Key words
Ambroxol Hydrochloride Solution for Inhalation/rat/lung tissue/pharmacokinetics/UPLC-MS/MS/content determination引用本文复制引用
基金项目
浙江大学实验技术研究项目(SYBJS202206)
出版年
2024
国家科技期刊平台
NSTL
万方数据