A New UPLC Method with Chemometric Design–Optimization Approach for the Simultaneous Quantitation of Brimonidine Tartrate and Timolol Maleate in an Eye Drop Preparation

Abstract

A new ultra-performance liquid chromatography (UPLC) with photodiode array was proposed for the quantitation of Brimonidine Tartrate (BRI) and Timolol Maleate (TIM) in eye drop using experimental design and optimization methodology. A 3 full factorial design was applied to uncover the effects of the selected factors and their interactions on the chromatographic response function for the optimization of experimental conditions in the development of a new UPLC method. As a result, the optimal chromatographic conditions giving a better separation and short analysis time were found to be 49.2°C for column temperature; 0.38 mL/min for flow rate and 56.7 % (v/v) for 0.1 M CHCOOH used in mobile phase. The elution of BRI and TIM was reported as 0.508 and 0.652 min within a short runtime of 1.5 min, respectively. Calibration graphs for BRI and TIM were obtained by the regression of the concentration on the peak area, which was detected at 246 and 298 nm, respectively. The method validation was performed by the analysis of the synthetic mixtures, intra-day and inter-day samples and standard addition samples. This study shows that the optimized and validated UPLC method is very promising and available for the quantification of BRI and TIM in an eye drop formulation.

Continuous Wavelet Transform Methods for the Simultaneous Quantification of Brimonidine Tartrate and Timolol Maleate in an Eye Drop Formulation

“…The simultaneous quantification of BRI and TIM in an eye drop formulation by were carried out without any chemical pre-treatment or any preliminary separation step. Compared to the UPLC method [23], the comparable assay results were obtained by applying mexh-CWT and Sym5-CWTmethods to the quantitation of the related active substances in the analyzed samples. The assay results indicate that these CWT approaches are very useful for the quality control and a routine analysis of the commercial eye drop formulation containing BRI and TIM drugs.…”

“…Then, then proposed wavelet transforms were successfully applied to the real samples. The results obtained by CWT methods were statistically compared with those obtained by the UPLC method developed in the literature [23] and good agreements were reported.…”

“…As it can be seen in Table 5, a good accordance with the acceptable standard deviation and relative standard deviation was reported for the analysis results obtained by applying the validated mexh-CWT and sym5-CWTmethods to the commercial eye drop formulation. Using one-way ANOVA test, the determination results of BRI and TIM in analyzed commercial sample were statistically compared with those of UPLC method in the literature [23]. It was observed that there is no difference between analysis by signal processing methods and UPLC approach.…”

DenTimol as A Dendrimeric Timolol Analogue for Glaucoma Therapy: Synthesis and Preliminary Efficacy and Safety Assessment

“…4 Because of this, the period after a dose where the drug is within its therapeutic concentration window in the anterior chamber is narrow, typically 4-5 hours. 5, 6 The remaining volume is flushed into systemic circulation where it can cause cardiovascular side effects of varying severity. 7–9…”

Ion-Selective Membrane Sensors for Determination of Brimonidine Tartrate in Bulk Powder, Pharmaceutical Eyedrops and Biological Fluids.

“…The literature survey reveals several analytical methods for quantitative estimation of BRD in body fluids and in pharmaceutical formulations by spectrophotometry [4][5][6][7][8][9][10], liquid chromatography [11][12][13][14][15][16][17][18][19][20][21] and electrochemical methods [22][23][24].…”