Validated spectrofluorimetric and spectrophotometric methods for the determination of brimonidine tartrate in ophthalmic solutions via derivatization with NBD‐Cl. Application to stability study

Abstract

Two simple, selective and accurate methods were developed and validated for the determination of brimonidine tartrate (BT) in pure state and pharmaceutical formulations. Both methods are based on the coupling of the drug with 4-chloro-7-nitro-2,1,3-benzoxadiazole in borate buffer (pH 8.5) at 70 °C and measurement of the reaction product spectrophotometrically at 407 nm (method I) or spectrofluorimetrically at 528 nm upon excitation at 460 nm (method II). The calibration graphs were rectilinear over the concentration ranges of 1.0-16.0 and 0.1-4.0 µg/mL with lower detection limits of 0.21 and 0.03, and lower quantification limits of 0.65 and 0.09 µg/mL for methods I and II, respectively. Both methods were successfully applied to the analysis of commercial ophthalmic solution with mean recovery of 99.50 ± 1.00 and 100.13 ± 0.71%, respectively. Statistical analysis of the results obtained by the proposed methods revealed good agreement with those obtained using a comparison method. The proposed spectrofluorimetric method was extended to a stability study of BT under different ICH-outlined conditions such as alkaline, acidic, oxidative and photolytic degradation. Furthermore, the kinetics of oxidative degradation of the drug was investigated and the apparent first-order reaction rate constants, half-life times and Arrhenius equation were estimated. The proposed methods are practical and valuable for routine applications in quality control laboratories for the analysis of BT.

A validated stability-indicating HPLC method for determination of brimonidine tartrate in BRI/PHEMA drug delivery systems

“…The detector wavelength was fixed at 246 nm and the peak areas were integrated automatically using the Hewlett–Packard ChemStation software program [16]. Other apparatus included an ultrasound generator and a SevenEasy pH meter (Mettler Toledo, USA) that was equipped with a combined glass–calomel electrode.…”

“…Various analytical methods have been reported for the determination of brimonidine tartrate, including electroanalytical method [14, 15], spectrophotometric method [16], highly sensitive gas chromatography/mass spectrometric assay [17], high-performance thin layer chromatography (HPTLC) [18], high-performance liquid chromatography (HPLC) [19–21], liquid chromatography–mass spectrometry (LC–MS) [22, 23] and high performance liquid chromatography-tandem mass spectrometry (HPLC-TMS) [24]. However, some of the above-described methods are limited in either low sensitivity or specificity.…”

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].…”

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

“…The literature survey showed that there were many analytical methods for the quantitative analysis of BRI and TIM, e.g. HPLC [5][6][7][8][9][10][11], spectrophotometry [12-14], flourimetric methods [15,16], high-performance thinlayer chromatography [17], capillary electrophoresis [18], gas chromatography-mass spectrometry [19], chemiluminescence method [20], membrane electrodes method [21] and extraction-photometric method [22]. This paper describes new implementations of the sym5-CWT and mexh-CWT methods to the UV absorption spectra for the simultaneous quantification of BRI and TIM in synthetic binary mixtures and commercial ophthalmic samples.…”