Sertraline HCl is an antidepressant compound for oral administration, belonging to the group of selective serotonin reuptake inhibitors (SSRI) in the brain. Chemically, sertraline is a secondary amine with a pKa value of 9.47.The analytical method employed for the determination of sertraline and its impurities (A, Band C) throughout the stability assays is generally based on reversed phase with ion-paring chromatography at acidic pH, employing 1-octane sulphonate and acetonitrile as organic modifier. The drawbacks of ion-pairing chromatography are generally known. One of them, the poor retention time reproducibility, is a source of problems during stability indicating assays. The availability of new stationary phases with new selectivities in reverse phase HPLC gave us the possibility of new separations avoiding these drawbacks. During the development also the replacement of acetonitrile with methanol was tested. Moreover, to our knowledge, there is no validated HPLC method including sertraline and these impurities described in the literature.A screening on RP stationary phases was conducted to explore different selectivities, including a wide range of polarities: C8, C18, cyano, PEG and amide. The best result was obtained with a Zorbax Bonus-RP column, which contains a polar amide group embedded in a C14 alkyl chain and has a triple end-capping. These characteristics yield in a reduction of the interactions between basic compounds and the silica support, improving peak shape and reducing the analysis time. Once the best stationary phase was chosen, a HPLC method was developed by means of an experimental design with four quantitative factors (organic proportion in the mobile phase, temperature, pH and buffer concentration) in order to find the best conditions which maximize the resolution between impurities A and B (positional isomers) and minimize the total run time.Optimal conditions for simultaneously determining sertraline and its impurities, being baseline separated in less than 10 min, were found with Zorbax Bonus-RP column (150 x 4.6 mm, 5 mm, Agilent Technologies), under isocratic conditions with 10 mM phosphate buffer (pH=2.8) and MeOH (63:37, v/v) at 50 ºC.This method has been successfully validated following ICH guidelines and it has proved to be reliable for the determination of sertraline and related impurities in tablets as pharmaceutical forms.
Development, optimization and validation of a stability indicating HPLC method for sertraline hydrochloride / A., Ferrarini; A. L., Huidobro; Pellati, Federica; C., Barbas. - STAMPA. - 1:(2009), pp. 120-120. (Intervento presentato al convegno Recent Developments in Pharmaceutical Analysis 13th International Meeting (RDPA 2009) tenutosi a Milano nel 9-12 Settembre 2009).
Development, optimization and validation of a stability indicating HPLC method for sertraline hydrochloride
PELLATI, Federica;
2009
Abstract
Sertraline HCl is an antidepressant compound for oral administration, belonging to the group of selective serotonin reuptake inhibitors (SSRI) in the brain. Chemically, sertraline is a secondary amine with a pKa value of 9.47.The analytical method employed for the determination of sertraline and its impurities (A, Band C) throughout the stability assays is generally based on reversed phase with ion-paring chromatography at acidic pH, employing 1-octane sulphonate and acetonitrile as organic modifier. The drawbacks of ion-pairing chromatography are generally known. One of them, the poor retention time reproducibility, is a source of problems during stability indicating assays. The availability of new stationary phases with new selectivities in reverse phase HPLC gave us the possibility of new separations avoiding these drawbacks. During the development also the replacement of acetonitrile with methanol was tested. Moreover, to our knowledge, there is no validated HPLC method including sertraline and these impurities described in the literature.A screening on RP stationary phases was conducted to explore different selectivities, including a wide range of polarities: C8, C18, cyano, PEG and amide. The best result was obtained with a Zorbax Bonus-RP column, which contains a polar amide group embedded in a C14 alkyl chain and has a triple end-capping. These characteristics yield in a reduction of the interactions between basic compounds and the silica support, improving peak shape and reducing the analysis time. Once the best stationary phase was chosen, a HPLC method was developed by means of an experimental design with four quantitative factors (organic proportion in the mobile phase, temperature, pH and buffer concentration) in order to find the best conditions which maximize the resolution between impurities A and B (positional isomers) and minimize the total run time.Optimal conditions for simultaneously determining sertraline and its impurities, being baseline separated in less than 10 min, were found with Zorbax Bonus-RP column (150 x 4.6 mm, 5 mm, Agilent Technologies), under isocratic conditions with 10 mM phosphate buffer (pH=2.8) and MeOH (63:37, v/v) at 50 ºC.This method has been successfully validated following ICH guidelines and it has proved to be reliable for the determination of sertraline and related impurities in tablets as pharmaceutical forms.
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