An improved and fully validated LC–MS/MS method for the simultaneous quantification of simvastatin and simvastatin acid in human plasma

A Review of Current Trends and Advances in Analytical Methods for Determination of Statins: Chromatography and Capillary Electrophoresis

“…Still, Apostolou and coworkers [75] suggested addition of protein precipitation reagent after the internal standard in order to ensure a more satisfying binding of internal standard molecules with plasma proteins, simulating the binding of proteins with analytes in real human plasma. A number of different protein precipitation reagents were tested [76].…”

“…Moreover, when low concentrations have to be detected it is necessary to use a large solvent volumes and sample preparation becomes time consuming and labor invasive. In order to reduce organic solvent consumption, sample volume and sample preparation time, Apostolou and coworkers [75] have presented a fully automated high-throughput two-step LLE-LC/MS/MS method for the quantification of simvastatin and its acid form using a robotic liquid handling workstation with 96-deepwell plates. Another fully automated high-throughput salting-out (SA) assisted LLE-LC/MS/MS method was introduced by Zhang and co-workers [82].…”

“…LC/MS/MS method developed by Apostolou and co-workers [75] consisted also of two periods combining both negative and positive ionization modes. Rosuvastatin has a pyrimidine ring and a carboxylic group in its structure, hence it could be detected either in positive or negative ionization mode.…”

“…In some cases one of the statins has been used as internal standard [73,75,77,84], while other works utilized internal standards of various structure, including hydrochlorothiazide [79], estrone [80], naproxen [90], gemfibrozil [91], pioglitazone [95] etc. The best internal standards for precise and accurate quantification in MS or tandem MS are stable-isotopelabeled standards.…”

“…Recently, Apostolou and co-workers [75] published fast and fully automated LLE-LC/MS/MS method, while Zhang and co-workers [82] presented a high-throughput saltingout assisted LLE-LC/MS/MS method for simvastatin in lactone and acid form. Both of methods were very fast with analytical runs less than two min and fairly sensitive with LOQ values around 0.1 ng/mL.…”