Validation strategy applied to a potenciometric method developed for determination of total fluoride in toothpastes

Y.S. CARO; G.M. SANTIAGO; M.S. CÁMARA; J.C. ROBLES; M.M. DE ZAN

Córdoba

Congreso; 1ra. Reunión Internacional de Ciencias Farmaceúticas; 2010

INTRODUCTIONThe validation of new analytical procedures, i.e, the proof of its suitability for the intended purpose, is a requirement that have been clearly documented by regulatory authorities. However the approach to validation is varied and opened to analyst interpretation (1). Several methodologies for chromatographic methods validation are available in literature, but not many for potentiometric procedures. Using the ICH guidelines as a basis we have selected the relevant parameters and acceptance criteria for designing experimental studies needed to validate a novel method for determination of total fluoride in toothpastes (2).MATERIALS AND METHODSSamples containing sodium fluoride (0.10%p/p) and monofluorphosphate (0.76%p/p) as active ingredients were hydrolyzed with perchloric acid at room temperature and total fluoride was determined using an ion selective electrode (ISE) by a potentiometric method employing TISAB solution. In this procedure 1.4 g of toothpaste were suspended in 20.0 mL of deionized water and 25.0 mL of 70% p/p perchloric acid were added. Solution was stirred 15 min and diluted to 250.0 mL in volumetric flask after neutralization with 25.0 mL of NaOH 10 mol L-1. For potentiometric measures 2.00 mL of sample solution were diluted to 20.0 mL with TISAB and solution potential was established with a fluoride ISE provided by OAKTON. TISAB solution was obtained by dissolving 58.5 g of NaCl, 61.4 g of sodium acetate and 0.30 g of sodium citrate in1.0L deionized water and adjusting pH to 5.5. The whole analytical procedure, including all the steps of the sample preparation, was applied in the determination of specificity, linearity, range, accuracy and precision. Spiking experiments for recovery and linearity investigations were performed in the whole working range using a synthetic mixture of matrix components as placebo and standards of sodium fluoride and monofluorphosphate.RESULTSNo matrix components interferences were detected during specificity assays performed by comparing average results of the response of reagents and placebo through a statistical t-test. Linearity was established in the range 4.0 to 12.0 mg L -1 by an F-test for residuals homoscedasticity and a lack of fit test. No statistical difference was obtained between the calibration set performed with pure standard solutions and matrix based calibration set, confirming the absence of ?matrix effect?. Main recovery was not different from 100 % at a 95% confidence level, with values ranging from 98.0 to 101.3% in spiked validation samples obtained for lowest, medium and highest calibration levels. Repeatability and intermediate precision were evaluated by applying an analysis of variance that showed no statistical difference between series performed in sextuplicate for medium calibration level in difference days and by different analysts. Relative standard deviation of the method resulted in 0.96%.CONCLUSIONSAn extended characterization and validation of the proposed method was carried out following international guidance obtaining excellent performance results. The procedure is simple, fast and efficient and may be applied in the routine quality control of toothpastes.ACKNOWLEDGMENTSThe authors thank UNL for financial support from ?Proyecto CAI+D 2009 Tipo II PI-12-62and Laboratorio LAFORMED S.A. for providing drugs and pharmaceuticalsREFERENCES(1) Ermer J.Validation in pharmaceutical analysis. PartI: An integrated approach.J Pharm Biomed Anal. 2001;24:755-767(2) Norma Oficial Mexicana PROY-NOM-219-SSA1.2002.