, Hülya SARI
SIMULTANEOUS SPECTROPHOTOMETRIC DETERMINATION OF TELMISARTAN AND HYDROCHLOROTHIAZIDE IN PHARMACEUTICAL PREPARATIONS BY RATIO SPECTRA DERIVATIVE METHOD
A. Hakan AKTAŞ*, Hülya SARI
Department of Chemistry, Faculty of Arts and Sciences, Süleyman Demirel University, 62300 Isparta, Turkey.
Background: As it is known, antihypertensive drugs are frequently used for the treatment of individuals with high blood pressure all over the world. This study aims is to precisely determine the active substances of telmisartan and hydrochlorothiazide, which are commercially sold as high blood pressure drugs in the market, and to use the ratio spectrum method for this purpose.
Method: All, solutions of the active ingredients of the drugs studied in the method were prepared in various concentrations. Subsequently, mixtures were prepared in accordance with the commercial drug sample, their spectra were taken by spectrophotometric method, and the spectrum ratio method was successfully applied to these data sets.
Results: The study revealed that the application of the ratio spectra first-order derivative spectrophotometric method yielded highly reliable outcomes in the spectrophotometric analysis of different combinations of telmisartan and hydrochlorothiazide.
Conclusion: The applied method can be used in the field of drug development.
Keywords: Active substances, derivative spectrophotometry, ratio spectra, Telmisartan.
INTRODUCTION
It is aimed to increase the efficiency by obtaining synergistic effects with the use of diuretic mixtures. The incorporation of thiazides and diuretics in drug combinations is a common practice owing to the benefits of low dosage and enhanced efficacy in managing hypertension. Combination of telmisartan (TEL) with hydrochlorothiazide (HCT) is used synergistic anti-hypertensive effects. Various methods including HPLC1-4, spectrophotometry5-8, LC-MS9, spectrofluorimetry10, and TLC10,11 for TEL and HCT analysis have been reported.The review of literature indicates that the analysis of these two drugs usually involves methods that are both costly and time-intensive. Also, not every research laboratory may have such expensive instrumental devices. The method we propose is made with a UV spectrophotometer, which is easily available in every laboratory, and analyzes can be done easily and can be expressed as a cheap method. The ratio spectra derivative method was also obtained as a result of the easy processing of the data obtained from the spectrum. For these reasons, it can be stated that the proposed method gives easy, cheap and reproducible results.
The research conducted by Salinas and his team12 has led to the development of a novel analytical approach for mixtures that generate consecutive spectra. This technique relies on the utilization of ratio spectra, which are frequently employed in contemporary practice.This technique is succinct and enables the straightforward quantification of active constituents by detecting the minimum or maximum points at the designated wavelengths. In recent times, Berzas Nevado et al.,13-14 and Dinç and Onur15-16 have employed this method to identify active compounds in pharmaceuticals.
The present study employed the ratio spectra derivative method to analyze a drug formulation comprising TEL and HCT, which pose a challenge for conventional UV methods due to their similar absorbance values. Similar to the approach employed by Salinas, analytical signals were gauged at wavelengths that corresponded to the maximum and minimum points in the first derivative values of the ratio spectra. Further, linear regression equations were established for both active components of the drug.
MATERIALS AND METHODS
Apparatus
All measurements were made with the UV 1700 PHARMASPEC SHIMADZU spectrophotometer. Absorbance measurements were performed under room temperature conditions with a pair of matching quartz cuvettes. The data groups taken in a computer environment were converted into graphs with Excel and performed following the operations.
Chemical and reagents
TEL and HCT and dosage forms (Telvis Plus® which contains 80 mg TEL and 12.5 mg HCT) were provided by Neutec Pharma International (Turkey). Methanol (Merck) used as a solvent has a chromatographic purity degree. All the chemicals used in the study were used in analytical purity.
Active ingredient solvents used
At the beginning of the experimental part of our research, stock solutions of the drug active ingredients we used in the study were prepared. For this, 100 ppm solutions of each of our active ingredients, which are weighed precisely in the laboratory, have been prepared. Then, these stock solutions were diluted to the ranges to be studied for spectrophotometric measurements.
Analysis of tablet
The commercial sample containing the active ingredients of the drug was weighed and at least ten tablets were crushed into powder in a mortar. Then, it was transferred to a balloon and the solution, which was sonicated with the solvent for at least 25 minutes to ensure the required dissolution, was completed to the volume to be used with the same solvent. It was observed that there were insoluble parts, these parts were filtered and washed with solvent and the solutions were combined.
RESULTS AND DISCUSSION
Ratio spectra were obtained as a result of dividing each of the spectra of the active ingredient of TEL pharmaceuticals obtained in different concentrations to the HCT spectrum in a certain concentration (Figure 1a).The ratio spectra were subjected to first derivative analysis (1DD) at an interval of Δλ=1 nm, using a scaling factor (SF) of /10 (Figure 1b). The resultant ratio spectra exhibited a maximum at 290 nm and a minimum at 257 nm, both of which were deemed appropriate for TEL quantification in the TEL+HCT mixture, as depicted in Figure 1b. In the experiments of the commercial product, 257 nm was selected from these values for the determination of this active ingredient. The reason for this is the lower RSD value and higher recovery average at the selected wavelength.As can be easily seen, the correlation coefficient at the selected 257 nm is closer to one and the slope is smaller. This situation is in perfect harmony with the low RSD values mentioned in The HCT standards were subjected to ratio spectra analysis by dividing each spectrum by the TEL spectrum at a specific concentration, as illustrated in Figure 3a. The ratio spectra were then subjected to first derivative analysis (1DD) at an interval of Δλ=1 nm, using a scaling factor (SF)=10 (Figure 3b). The resulting ratio spectra exhibited a maximum at 280 nm and a minimum at 264 nm, both of which were deemed appropriate for HCT quantification in the HCT+TEL mixture, as depicted in Figure 3b. Additionally, Figure 4a and Figure 4b present the regression equations and correlation coefficients derived for the two wavelengths assessed in the ratio spectra. For the reasons we mentioned above for Telmisartan, 264 nm was also selected for Hydrochlorothiazide, and successful results were obtained. Table 1 presents the average recoveries and corresponding relative standard deviations obtained for the synthetic mixtures prepared in the laboratory using the applied method, which were deemed highly satisfactory. In such study, the divisor concentration is a crucial factor. In this study, the standard spectra were divided by 25 ppm TEL and 8 ppm HCT concentrations, which were deemed optimal for the quantification of TEL and HCT, respectively.
Finally, the application of the method was tested on a commercial sample. The cumulative results are shown in Table 2.
CONCLUSION
It has been shown that the ratio spectrum method we proposed for quantitative measurement of TEL and HCT prepared synthetically in the laboratory environment gives repeatable and accurate results without any pretreatment. It has been concluded that the proposed method can be applied routinely in drug development laboratories.
CONFLICT OF INTEREST
There is no conflict of interest.
AUTHOR’S CONTRIBUTION
The authors continued to work by acting jointly at each stage of the study.
ACKNOWLEDGEMENTS
We would like to thank Süleyman Demirel University Institute of Natural Sciences for enabling such a study to be carried out.
REFERENCES