Zero-order UV spectrophotometric system for the determination of olmesartan medoxomil and metoprolol succinate in tablets

Abstract

A zero-order UV spectrophotometric system for the simultaneous determination of olmesartan medoxomil and metoprolol succinate in tablet form, with analytical wavelengths of approximately 255 nm for olmesartan medoxomil and approximately 215.5 nm for metoprolol succinate using distilled water as solvent.

Description

Application area of ​​the invention

[0001] The invention relates to analytical measurement systems for pharmaceutical quality control, in particular a zero-order UV spectrophotometric method with distilled water for the simultaneous quantification of olmesartan medoxomil (OLM) and metoprolol succinate (MET) in combination preparations with ICH-compliant validation. Background of the invention

[0002] Fixed-dose combinations of olmesartan medoxomil and metoprolol succinate are frequently used in hypertension therapy. This necessitates reliable, rapid, and cost-effective analytical methods for routine content determination and ensuring consistency in production and quality control laboratories. Existing UV spectrophotometric methods for determining OLM and MET include simultaneous equation and dual-wavelength strategies. However, many of these methods rely on organic solvents, less selective wavelength pairs, or require more complex data processing, which can limit robustness and suitability for routine use. ICH Q2(R1) establishes validation criteria such as specificity, linearity, accuracy, precision, limits of detection, limits of quantification, and robustness for analytical methods and serves as a basis for method development and acceptance criteria.The literature shows that UV spectrophotometry under Beer-Lambert conditions can achieve high linearity with correlation coefficients close to 0.999 when the methods are optimized and validated. However, matrix effects and spectral overlaps must be carefully considered. Therefore, there is a need for a zero-order, water-based UV method with analytically differentiating wavelengths that minimizes solvent hazards and complexity while ensuring ICH-compliant performance for OLM and MET tablets. Summary of the invention:

[0003] The invention provides a zero-order UV spectrophotometric system that uses distilled water as a solvent and fixed analytical wavelengths of approximately 255 nm for OLM and approximately 215.5 nm for MET to quantify the active ingredients in combined tablet matrices without organic solvents. For both active ingredients in the concentration range of approximately 2–10 µg / ml, the method exhibits linearity according to the Lambert-Beer law with correlation coefficients close to 0.999, a recovery rate of approximately 99–101%, and a precision between and within one day with a mean relative standard deviation (%RSD) of less than 2%. It thus meets the ICH validation criteria for linearity, accuracy, precision, specificity, and robustness.

[0004] In one embodiment, spectral scanning confirms the selection of the zeroth-order maximum to minimize overlaps. Calibration and sample analysis are then performed using simple aqueous extraction. This verifies the selectivity for common auxiliary substances and the robustness to short wavelengths and operator errors. The method reduces costs and environmental impact compared to solvent-intensive HPLC while enabling rapid routine analyses. It is therefore a practical solution for quality control wherever rapid screening or release testing is required and matrix interferences can be controlled. Detailed description

[0005] The system uses a UV / VIS spectrophotometer that scans the 200–400 nm range with a 1 nm resolution. Distilled water serves as the diluent for standard and sample solutions to avoid spectral artifacts caused by organic solvents in routine quality control workflows. Zero-order absorption maxima are determined by scanning pure standards: OLM exhibits a major maximum near 255–258 nm in aqueous media, while MET shows strong absorption in the lower UV range. For MET, an analytical wavelength of approximately 215.5 nm is chosen to achieve high sensitivity while also verifying specificity against the background of excipients. Calibration curves are generated for each analyte in the concentration range of approximately 2–10 µg / mL by plotting absorbance against concentration.The resulting regression curves show correlation coefficients close to 0.999, which confirms compliance with the Lambert-Beer law within the specified range.

[0006] Sample preparation includes precise pulverization of the tablets, aqueous extraction under ultrasonic treatment or stirring, and filtration to obtain a clear solution within the calibrated concentration range. If necessary, the solution is diluted with distilled water to maintain absorbance values ​​within the optimal range (typically below 1.0 AU). Specificity is demonstrated by comparison of spectra of standards, blank diluent, and placebo matrix. The absence of interfering absorbance at 255 nm and 215.5 nm is confirmed under method conditions, in accordance with ICH recommendations for the specificity evaluation of spectrophotometric methods. Linearity is confirmed across the entire target range. Residual plots show no significant curvature, and confidence intervals for slope and intercept are recorded to support routine application.Weighting can be evaluated if necessary, but is generally not required within the specified range. Accuracy is determined by standard addition or spiking studies at various concentrations within the working range. Mean recoveries are approximately 99–101%, and acceptance meets ICH-typical criteria for analytical methods that allow determination close to 100% of the declared value. Precision is confirmed by repeatability (six replicates) and comparability (on different days and / or with different analysts). The relative standard deviation (%RSD) is consistently below 2%, which is consistent with published UV methods for small molecules under controlled conditions. Robustness and stability are assessed by targeted, small variations such as wavelength shifts of ±1 nm, minor changes in path length or sample handling, and by changing analysts / instruments.The results remain within the acceptable limits. This complies with the evolving ICH Q14 guideline, which stipulates that robustness be considered during the development phase prior to formal validation. System suitability is ensured through tests such as basic stability, lamp energy, and a standard absorption repeatability test to guarantee the instrument's operational readiness before analysis. Criteria include the relative standard deviation (%RSD) of replicates of standard absorptions within predefined limits. The method documentation follows the ICH Q2(R1) structure for validation reports and describes in detail specificity, linearity, range, accuracy, precision, limits of detection and quantification (where applicable), and robustness. This enables regulatory approval for quality control of combined OLM-MET tablets.The cases of simultaneous UV determination of MET and OLM described in the literature demonstrate the feasibility of zero-order aqueous wavelength selection methods. This system focuses on the use of distilled water as a solvent and the differentiation of wavelength pairings with strong performance characteristics according to ICH criteria.

Claims

[1] A zero-order UV spectrophotometric system for the simultaneous determination of olmesartan medoxomil and metoprolol succinate in tablet form, with analytical wavelengths of approximately 255 nm for olmesartan medoxomil and approximately 215.5 nm for metoprolol succinate using distilled water as solvent. [2] System according to claim 1, wherein the calibration linearity for each analyte in the range of approximately 2-10 µg / ml has been demonstrated with correlation coefficients close to 0.999, which corresponds to the Beer-Lambert law under the specified conditions. [3] System according to claim 1, wherein the validation demonstrates the accuracy with recovery rates of approximately 99-101% and the precision with mean relative standard deviations (%RSD) of less than 2% between days and within a day in accordance with the ICH validation requirements for analytical methods. [4] System according to claim 1, wherein robustness and stability are maintained even with minor, targeted variations of the wavelength and the analyst / instrument, and the specificity towards tablet excipients is confirmed at the selected wavelengths.