Stability study of simvastatin under hydrolytic conditions assessed by liquid chromatography.
In this work, a liquid chromatography stability-indicating method was developed and applied to study the hydrolytic behavior of simvastatin in different pH values and temperatures. The selected chromatographic conditions were a C18 column; acetonitrile-28 mM phosphate buffer solution, pH 4 (65 + 35) as the mobile phase; 251 degrees C column temperature; and flow rate 1 mL/min. The developed method exhibited an adequate repeatability and reproducibility (coefficient of variation 0.54 and 0.74%, respectively) and a recovery higher than 98%. Furthermore, the detection and quantification limits were 9.1 x 10(-7) and 2.8 x 10(-6) M, respectively. The degradation of simvastatin fitted to pseudo-first order kinetics. The degradation was pH dependent, being much higher at alkaline pH than at acid pH. Activation energy, kinetic rate constants (k) at different temperatures, the half life (t1/2) and the time for 10% degradation to occur (t90) values are also reported.
Alvarez-Lueje
Alejandro
A
University of Chile, Bioelectrochemistry Laboratory, Chemical and Pharmaceutical Sciences Faculty, PO Box 233, Santiago 1, Chile. aalvarez@ciq.uchile.cl
Valenzuela
Christian
C
Squella
Juan Arturo
JA
Núñez-Vergara
Luis Joaquín
LJ
D000097:Acetonitriles / Q000737:chemistry; D002021:Buffers; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D002845:Chromatography; D002853:Chromatography, Liquid / Q000379:methods*; D002855:Chromatography, Thin Layer; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000032:analysis / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D010710:Phosphates / Q000737:chemistry; D015203:Reproducibility of Results; D019821:Simvastatin / Q000032:analysis* / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
D000097:Acetonitriles; D002021:Buffers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010710:Phosphates; D019821:Simvastatin; C032159:acetonitrile