Titrimetric and spectrophotometric determination of doxycycline hyclate using bromate-bromide, methyl orange and indigo carmine

One titrimetric and two indirect spectrophotometric methods are described for the determination of doxycycline hyclate (DCH) in bulk drug and in its formulations. The methods use bromate-bromide, methyl orange and indigo carmine as reagents. In titrimetry (method A), DCH is treated with a known excess of bromate- -bromide mixture in acid medium and the residual bromine is back titrated iodometrically after the reaction between DCH and in situ bromine is ensured to be complete. In spectrophotometric methods, the excess of bromine is estimated by treating with a fixed amount of either methyl orange (method B) or indigo carmine (method C) and measuring the change in absorbance either at 520 or 610 nm. Titrimetric method is applicable over 1-8 mg range and the calculations are based on a 1:2 (DCH:bromate) stoichiometric ratio. In spectrophotometry, the calibration graphs were found to be linear over 0.25-1.25 and 1.0-5.0 μg mL-1 for method B and C, respectively, with corresponding molar absorptivity values of 2.62×105 and 6.97×104 L mol-1 cm-1. The accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different levels of DCH.