Titrimetric and sensitive spectrophotometric methods for the assay of quetiapine fumarate in pharmaceutical formulations

Abstract

Quetiapine fumarate (QTF) is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), and dopamine type 2 (D2) receptors. Titrimetric and spectrophotometric assay of quetiapine fumarate (QTF) using perchloric acid and acetic acid as reagents are described. The first method (method A) is a non-aqueous titrimetric method and is based on the titration of QTF in glacial acetic acid with 0.01M acetous perchloric acid using crystal violet as indicator. In the second method (method B), QTF has been measured in 0.1M acetic acid spectrophotometrically at a wavelength of 222 nm. The titrimetric method was applicable over the range of 2.0 - 20.0 mg of QTF. The reaction stoichiometry of 1:3 is obtained which served as the basis for calculation. In spectrophotometry, Beer?s law was obeyed over the concentration range of 1.25 - 15.0 ?g mL-1. The linear regression equation of the calibration graph was A = 0.0115 + 0.0673 C with a regression coefficient (r) of 0.9986 (n=7). The apparent molar absorptivity was calculated to be 4.25 ? 104 L mol-1cm-1 and the Sandell sensitivity was 0.0145 ?g cm-2. The limits of detection (LOD) and quantification (LOQ) calculated as per the ICH guidelines were 0.07 and 0.21 ?g mL-1, respectively. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different levels of QTF. The intra-day and inter-day relative standard deviation (%RSD) were in the range of 0.99 - 2.88 and 1.65 - 2.32%, for method A and method B, respectively, with an acceptable percentage relative error (%RE) < 2%. The methods were successfully applied in the determination of QTF in two different brands of tablets with good accuracy and precision and without detectable interference by excipients. The methods have demonstrated to be simple and easy to apply in routine usage and do not need any costly instrumentation. Therefore, the reported procedures are advantageous and can be adopted in routine quality control laboratories in the developing or under developed countries.