A rapid and sensitive LC-MS/MS method has been developed and fully validated for simultaneous quantification of aspirin (ASP), salicylic acid (SLA), rosuvastatin (RVT), rosuvastatin lactone (RVL) and N-desmethyl rosuvastatin (DM RVT) in human plasma using a polarity switch with 400 μL of sample human blank plasma. Deuterated Internal Standards (IS) were used for each analyte. The solid phase extraction was used as sample preparation techniques. Chromatograph was monitored on a zorbax SB-phenyl column with a gradient mode with API-5500 triple quadrupole mass spectrometer as detector. The assay method was validated over the concentration range of 0.1-25 ng/mL for RVT; 50-10000 pg/mL for RVL and DMRVT; 5-2000 ng/mL for ASP; and 0.1-8 μg/mL for SLA. Intra and inter-day precision and accuracy were within acceptance limit. The mean recovery was >85% for all analytes. The analytes were stable at RT for 6 h in solution, at 2-8°C for 15 days in solution, for RT for 6 h in plasma, RT for 2 h in blood, till 3 freeze/thaw cycles, 104 h in auto-sampler at 6°C. This proposed method can be used for measurement of reliable concentration for dossier submission.