Assay Of Enantiomeric Purity And Residual Solvents In R-rabeprazole Sodium

R(+)-rabeprazole sodium is a new proton pump inhibitor(PPI).Compared to the raceme and S(-)-isomer of rabeprazole sodium,R(+)-rabeprazole sodium has stronger pharmacological action,smaller effective dose,longer half-life of the metabolites,better curative effects and lower adverse effects.R(+)-rabeprazole sodium hasn’t been permitted to launch in China at present,it is important to develop a novel process for preparing high purity R(+)-rabeprazole sodium and high-efficiency assay methods for controlling the quality of the target product.In this paper,the methods for determination of enantiomer purity and residual solvents in target product were systematically researched.In order to assay enantiomer purity of R(+)-rabeprazole sodium,a method of High Performance Liquid Chromatography(HPLC)was used,a chiral column was chosen to separate R(+)-rabeprazole sodium and S(-)-rabeprazole sodium,effects of measuring wavelength and components of the mobile phase on resolution were investigated,the optimized conditions were obtained as follows: a chiral column,CHIRALPAK-AGP column(2.5um,100 mm × 4mm),packed with α1-acid glycoprotein immobilized on silica gel was chosen as stationary phase,a mixed solution of acetonitrile and phosphate buffer(p H 6.0)in a 10:90 ratio(v/v)was used as the mobile phase,and UV detection at 285 nm was utilized.There is good linear relation between the peak area and concentration of S-rabeprazole sodium from 0.0384μg/m L to 0.576μg/m L,the correlation coefficient(R2)is 0.9997.The detection limit(3S/N)of S-rabeprazole sodium is 0.2ng.The recoveries measured by standard addition method at three different concentrations are all in the range of 91%-102%,showing high accuracy.In order to assay the contents of residual solvents in R(+)-rabeprazole sodium,a method of Headspace Gas Chromatography was used,a capillary column was chosen to separate residual solvents,the effect of temperature programming on resolution was investigated,the optimized conditions were obtained as follows: headspace equilibrium temperature and duration was set as 90℃ and 20 min respectively;A Agilent DB-624 capillary column(30m ×0.32mm×1.8μm)was chosen;The temperature program for chromatographic column included keeping 8min at 40℃,then rising to 240℃ with the rate of 20℃/min and keeping 20min;The temperature of the injection port was maintained at 150℃;FID detector was utilized and the temperature was held at 250℃,Nitrogen was served as carrier gas;Under this condition,there are good resolutions to adjacent residual solvents,an excellent linear relation between the peak area and concentration of each solvent,low LOD,nice repeatability and high accuracy.It is suitable to be used for controlling the residual solvents in the target product.