Micro and nanogram determination of lamotrigine in pharmaceuticals by visible spectrophotometry using bromophenol blue

摘要

Three reliable, rapid, highly sensitive and selective methods have been developed and validated for the determination of lamotrigine (LMT) in pure drug and in tablets. The first method (method A) is based on the formation of chloroform extractable ion-pair complex between LMT and bromophenol blue (BPB) at pH 1.44+0.01 with a wavelength of maximum absorption at 420 nm. In the second (method B) and third (method C) methods, the drug-dye ion pair is dissolved in either ethanolic H2SO4 and resulting acid form of the dye is measured at 420 nm or ethanolic KOH and the resulting base form of the dye is measured at 600 nm. All variables affecting the drug-dye complex formation and its extraction into CHCl3 have been investigated and conditions optimized. Beer's law was obeyed over 2.5-25 μg mL~(-1), 50-400 ng mL~1 and 10-80 ng mL~(-1), for method A, method B and method C, respectively. The calculated molar absorptivity values are 7.26 × 10~3, 5.4 x10~5 and 2.6 × 10~6 1 mol~(-1) cm~(-1), respectively, for methods A, B and C; and the corresponding Sandell sensitivities are 0.0353, 0.0005 and 0.0001 ug cm~(-2). The limits of detection (LOD) and quantification (LOQ) have also been reported. The stoichiometry of the formed ion-pair complex was found to be 1:1 .for method A, and the stability constant is also calculated. The accuracy and precision of the methods were evaluated on intra-day and inter-day basis; and the relative error (RE) and the relative standard deviation (RSD) were < 2.0% and < 1.4%, respectively. The proposed methods were successfully applied for the determination of LMT in bulk powder and in tablets.