Simultaneous determination of drugs with different physicochemical properties necessitates thorough research and careful selection of high‐performance liquid chromatography conditions. In the present study, various concepts of high‐performance liquid chromatography method development for this aim have been discussed. Moreover, the work was motivated by the advantages of utilizing different chaotropic anions as a new promising approach to overcome the limitations of ion‐pairing agents commonly used for this purpose. Based on log P values, atorvastatin (log P = 6.36) and lisinopril (log P = –1.22) were chosen as representative examples for lipophilic and hydrophilic drugs, respectively. Several simple, economic, fast, and reliable high‐performance liquid chromatography methods were developed for their simultaneous analysis and are presented in a comparative manner, highlighting their advantages and limitations. Peak elution profile showed satisfying retentions and resolution about 3. Photo‐diode array calculations were exploited for identifying the molecules by their ultra‐violet spectra and peak purity, calculated and presented as rectangular‐shaped ratio grams. The linearity check showed excellent results and satisfactory system suitability parameters of both peaks. This confirms the investigation results and conclusions for the influence of the chaotropic salts on N‐containing molecules, by increasing their retentivities, and improving peak shapes, even on different quality columns without end‐capping and base‐deactivating of separation matrixes.
Our main target and concept was to develop a method for the determination of the most prescribed antilipemic drug, atorvastatin, together with its related substances, with a single sample preparation and during a single chromatographic run, in the shortest possible period of time, with the lowest possible mobile phase consumption. A new rapid, simple chromatographic method for the determination of atorvastatin and its main specified impurities was developed, using different chromatographic columns. With this new concept of a mobile phase and a powerful core–shell, or a superficially porous silica-based column, satisfactory results for targeted parameters, such as critical peak resolution, run time length, and column backpressure, were achieved. The analysis is performed within a run duration of less than 15 minutes, which is about six times shorter than the official European Pharmacopoeia method. The chromatogram performances suggests that the method limit of quantification (LOQ) can be about 7 times lower, and the limit of detection (LOD) about 20 times lower, using an injection volume of only 2 µl. This was confirmed by the performed method validation in accordance with the International Conference on Harmonization (ICH) guideline for the validation of analytical procedures Q2(R1), where the selectivity, linearity, accuracy, precision, limit of quantification, and limit of detection were tested and confirmed.
Two simple, rapid and green spectrophotometric methods are described for the determination of lisinopril medicines. The determination is based on the reaction of the primary amino group of the lisinopril with ninhydrin in aqueous medium (Method I) and reaction on the carboxylic group of the lisinopril with copper (II) sulfate (Method II). For both methods, optimal spectrophotometric conditions were established. The linear relationship was found between absorbance at λmax and concentration of drug in the range 40–60 µg/mL (Method I) and 0.592–2.072 mg/mL (Method II). Regression analysis of Beer’s law plot at 400 nm yielded the regression equation, y = 7.4929x – 0.0545 (Method I) and at 730 nm y = 0.0443x – 0.0832 (Method II). High values of correlations coefficient (R2 = 0.9917 (Method I) and R2 = 0.999 (Method II)) and small values of intercept validated the linearity of calibration curve and obedience to Beer’s law. The LOD and LOQ values were calculated to be 6.91 µg/mL and 23.01 µg/mL respectively (Method I) and 0.11 mg/mL and 0.36 mg/mL respectively (Method II). Intra-day and inter-day accuracy and precision were in acceptable limits. The proposed methods were applied for the quantification of lisinopril in tablets pertaining to three commercial formulations. Analytical eco-scale for greenness assessment of the proposed spectrophotometric methods showed that both methods correspond to excellent green analysis.
Aim. The research aims at developing a fast, simple, reliable spectrophotometric method according to "green" chemistry principles for the determination of lisinopril in pure substance and in drugs presented on the Ukrainian market. Materials and Methods. Chemical reference standard of lisinopril dihydrate (Sigma-Aldrich, ³98%, HPLC), methanol R (Honeywell Riedel-de Haen™, 99.9%), tablets of Lisinopril-Astrapharm 10 mg), Lisinopril-KRKA 10 mg (Slovenia) and Lisinopril-Teva 10 mg (Germany) were used in this study. Double-beam scanning spectrophotometer "Shimadzu UV-1800" (Japan) connected with software package UV-Probe 2.62 were used for measurements. Absorbance of the solutions in the UV region were recorded in 1 cm quartz cells vs. methanol R. Laboratory electronic balance RAD WAG AS 200 / C, ultrasonic bath Sonorex Digitec DT100H and measuring glassware of grade A were used. Statistical processing and determination of validation parameters were performed in accordance with the requirements of State Pharmacopoeia of Ukraine 2.0 and ICH Q2. Results and Discussions. The spectrophotometric method for the determination of lisinopril by direct measurement of the absorbance of the tested solutions in the ultraviolet region of the spectrum has been developed (lmax=212 nm). Validation parameters including linearity, range of application, specificity, accuracy, precision, limit of detection and limit of quantification, robustness were calculated for the proposed analytical procedure. The correctness of the analytical method was proved by calculating the complete uncertainty of the latter. The calculated uncertainty of sample preparation (DSP) for the determination of lisinopril in tablets was 2.46%. It was established that the maximum contribution to the uncertainty of sample preparation for operations of the quantification of lisinopril in tablets, make the operations of lisinopril CRS sampling and aliquots pipetting. The total uncertainty of the analytical procedure (DAs) in the analysis of the drug was 2.56%. The predicted complete uncertainty of the analysis results did not exceed critical values (DAs=2.56 % £ maxDAs=3.2 %), the method is correct. The specificity is proved by the absence of interfering influence of excipients due to nonoccurence of absorption at the analytical wavelength in the analysis of methanolic extract of placebo-tested tablets, Beers law was obeyed in the ranges of 20-100 mg / ml. The least squares method was used for statistical processing of the results. Regression analysis yielded the following calibration equation: y=26,791x-0,4398. The limit of detection and the limit of quantification were 2,3 і 6,9 mg/ml. Robustness of the method was estimated by studying of absorbance stability changes of tested solutions over time. Robustness was assessed by studying the absorbance stability of the tested solutions over time. It was found that freshly prepared solutions should be used within 100 min. Developed procedure for lisinopril determination in pure substance and tablet dosage form proved to be an excellent green analysis according to analytical eco-scale. Conclusions. Fast, simple, reliable, cost-effective, in accordance with the principles of "green" chemistry spectrophotometric method for determination of lisinopril in pure substance and tablets has been proposed. Validation of the analytical procedure on the parameters of linearity, application range, specificity, accuracy, precision, robustness, limit of detection and limit of quantification was carried out. The complete uncertainty of the analytical procedure at the level of 2.56% was obtained, which proves the possibility of obtaining correct analysis results in other laboratories.
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