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

作　　者：平丽 洪雅雯 吴玥 PING Li;HONG Yawen;WU Yue(College of Pharmaceutical Sciences,Zhejiang University·Center for Drug Safety Evaluation and Research of Zhejiang University,Hangzhou,Zhejiang,China 310058)

机构地区：[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

出　　处：《中国药业》2024年第14期54-57,共4页China Pharmaceuticals

基　　金：浙江大学实验技术研究项目[SYBJS202206]。

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 C_(18)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10~1000 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=0.9986,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(t_(1/2))为4.33 h,峰浓度(C_(max))为3997.40 ng/g,药-时曲线下面积(AUC_(0-t))为4311.88(ng·h)/g,平均滞留时间(MRT_(0-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。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 C_(18) column(100 mm×2.1 mm,1.7μm),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 5μL.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 10-1000 ng/mL(r=0.9986,n=7).The results of precision,stability,recovery tests and matrix effect all met the methodological requirements.The half-life(t_(1/2))was 4.33 h,the peak concentration(C_(max))was 3997.40 ng/g,the area under the plasma concentration-time curve(AUC_(0-t))was 4311.88(ng·h)/g,the mean residence time(MRT_(0-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 

分 类 号：R965[医药卫生—药理学]