HPLC-MS/MS Method For The Determination Of Sodium Cromoglycate Concentration In Human Plasma And Its Pharmacokinetic Studies

Objective:To develop a high performance liquid chromatography(HPLC) coupled with tandem mass spectrometry quantitative detection method for determining the concentrations of Sodium Cromoglycate in human plasma.And to evaluate the pharmacokinetics of naristillae and intranasal spraying agent of Sodium Cromoglycate.Methods:1.A C₁₈ column was used to separate Sodium Cromoglycate in plasma with a mobile phase of a mixture of ammonium-methanol(involves 50%acetonitrile)(15:85) at a flow rate of 0.4mL·min^-1.Electronic spray ionization(ESI) and multiple-reaction monitoring(MRM) was used for the determinition of Sodium Cromoglycate in human plasma.2.20 Chinese healthy volunteers were screened according to two period cross-over design test and 4mL blood was collected before and 0.17,0.33,0.5,0.67,0.83,1.0,1.25,1.5,2.0, 3.0,4.0,5.0 h after a single oral dose Naristillae and intranasal spraying agent of Sodium Cromoglycate.The Sodium Cromoglycate in plasma was determined by HPLC-MS/MS methods and its main pharmacokinetic parameters were calculated and evaluated by DAS 2.0 software.To Evaluate bioequivalence of test preparation and reference preparation.Results:1.The linear range of the standard curve of Sodium Cromoglycate was 0.3～20 ng·mL^-1, and the minimum concentration of detection was 0.3ng·mL^-1.The extraction recovery was more than 94.1%,intra-day and inter-day RSD were less than 14.3%.2.After a single dose of Sodium Cromoglycate,the main pharmacokinetics parameter of naristillae,intranasal spraying agent were as follows,t_1/2(1.815±0.535)h,(1.592±0.518) h;T_max(0.467±0.116)h,(0.442±0.147)h;C_max(9.789±4.662)ng·ml^-1,(10.877±4.047)ng·ml^-1;AUC_(0-1),(11.519±3.461)ng·ml^-1·h,(12.629±4.228)ng·ml^-1·h,F 93.6%±13.8%.Conclusions:1.To establish a HPLC-MS/MS method for determining the concentrations of Sodium Cromoglycate in human plasma.The method is sensitive,fast and accurate.It is suitable for therapeutic drug monitoring and human pharmacokinetic studies of Sodium Cromoglycate..2.It can be concluded that the disposition of Sodium Cromoglycate in human were fitted with three-compartment model.The test preparation and reference preparation have bioequivalence.