THE SIMULTANEOUS SPECTRAL DETERMINATION OF CANDESARTAN CILEXETIL AND HYDROCHLOROTHIAZIDE IN TABLETS USING THE TRIVARIATE CLASSICAL LEAST SQUARES METHOD

Year 2024, , 803 - 810, 10.09.2024

Asiye Üçer , Özgür Üstündağ , Uğur Saklı , Erdal Dinç

https://doi.org/10.33483/jfpau.1441955

Abstract

Objective: Candesartan cilexetil (CDS) is a member of the sartan group of drugs and is widely used to lower blood pressure. Hydrochlorothiazide (HCT) is the most commonly used diuretic group of drugs and is prescribed together with candesartan cilexetil in cases where blood pressure cannot be reduced. Pharmaceutical preparations containing these two active compounds in combination are preferred today to provide a more effective pharmacological effect. Therefore, it is of great importance to determine the quantities of these combined pharmaceutical preparations with new analytical methods that are fast, easy, and sensitive in quality control and routine analysis. In this study, a new trivariate classical least squares calibration method (TCLS) was developed for the simultaneous quantification of candesartan cilexetil (CDS) and hydrochlorothiazide (HCT) in binary mixtures and commercial tablets without using a preliminary separation step.
Material and Method: CDS and HCT compounds were kindly donated by National Pharm Ind., Turkey. HPLC-grade methanol (J.T. Baker, Netherlands) was used as a solvent for the spectrophotometric analysis. In the application of the TCLS method, the determination and quantification of CDS and HCT were carried out using UV spectrophotometric measurements with 1 cm quartz cells in the 200-310 nm spectral region (slit range 2 nm). The newly developed TCLS method was tested using a validation set consisting of eight synthetic mixture solutions within the working ranges of 4.0-20.0 μg/ml for CDS and HCT. Simultaneous quantification analyses of CDS and HCT were performed on ATACAND PLUS® Tablet supplied by Astra Zeneca İlaç Ltd Şti.
Result and Discussion: The method is based on the application of TCLS to the absorbance measurements at three different wavelength points (223.5, 240.0, and 268.5 nm). The absorptivity values (µg-1mlcm-1) of pure CDS and pure HCT were 6.67x10-2, 2.76x10-2, 2.33x10-2, and 11.41x10-2, 0.46x10-2, 6.42x10-2 at the selected wavelengths, respectively. Recovery values and relative standard deviation values were calculated as 97.2% and 1.61% for CDS and 99.7% and 3.67% for HCT, respectively. This method was successfully applied to the spectrophotometric quantitative analysis of tablets containing CDS and HCT, and then, a good agreement was reported.

Keywords

Angiotensin II receptor antagonists, candesartan cilexetil, hydrochlorothiazide, quantitative tablet analysis, trivariate classical least squares method

ÜÇ DEĞİŞKENLİ KLASİK EN KÜÇÜK KARELER YÖNTEMİ KULLANILARAK TABLETLERDE KANDESARTAN SİLEKSETİL VE HİDROKLOROTİAZİDİN EŞZAMANLI SPEKTRAL TAYİNİ

Abstract

Amaç: Kandesartan sileksetil (CDS), sartan ilaç grubuna ait olup, kan basıncını düşürmek amacıyla yaygın olarak kullanılmaktadır. Hidroklorotiazid (HCT) en sık kullanılan diüretik ilaç grubudur ve kan basıncının düşürülemediği durumlarda kandesartan sileksetil ile birlikte reçete edilir. Bu iki aktif bileşiğin kombinasyon halinde bulunduğu farmasötik preparatlar, günümüzde daha etkili bir farmakolojik etki sağlamak amacıyla tercih edilmektedir. Bu nedenle, bu kombine farmasötik preparatların miktarlarının, kalite kontrol ve rutin analizlerde hızlı, kolay ve hassas yeni analitik yöntemlerle belirlenmesi büyük önem taşımaktadır. Bu çalışmada, ikili karışımlarda ve ticari tabletlerde kandesartan sileksetil (CDS) ve hidroklorotiyazidin (HCT) bir ön ayırma adımı kullanılmadan eş zamanlı ölçümü için yeni bir üç değişkenli klasik en küçük kareler kalibrasyon yöntemi (TCLS) geliştirildi.
Gereç ve Yöntem: CDS ve HCT bileşikleri National Pharm Ind., Türkiye tarafından bağışlanmıştır. Spektrofotometrik analiz için solvent olarak metanol (J.T. Baker, Hollanda) kullanıldı. TCLS yönteminin uygulanmasında CDS ve HCT'nin belirlenmesi ve nicelendirilmesi, 200-310 nm spektral bölgede (slit aralığı 2 nm) 1 cm'lik kuvars hücrelerle UV spektrofotometrik ölçümler kullanılarak gerçekleştirildi. Yeni geliştirilen TCLS yöntemi, CDS ve HCT için 4.0-20.0 μg/ml çalışma aralıklarında sekiz sentetik karışım çözeltisinden oluşan bir doğrulama seti kullanılarak test edildi. Astra Zeneca İlaç Ltd Şti tarafından sağlanan ATACAND PLUS® Tablet üzerinde CDS ve HCT'nin eş zamanlı miktar tayini analizleri yapıldı.
Sonuç ve Tartışma: Yöntem, TCLS'nin üç farklı dalga boyu noktasında (223.5, 240.0 ve 268.5 nm) absorbans ölçümlerine uygulanmasına dayanmaktadır. Saf CDS ve saf HCT'nin absorptivite değerleri (μg-1mlcm-1) seçilen dalga boylarında sırasıyla 6.67x10-2, 2.76x10-2, 2.33x10-2 ve 11.41x10-2, 0.46x10-2, 6.42x10-2 idi. Geri kazanım değerleri ve bağıl standart sapma değerleri CDS için sırasıyla %97,2 ve %1,61, HCT için ise %99,7 ve %3,67 olarak hesaplandı. Bu yöntem, CDS ve HCT içeren tabletlerin spektrofotometrik kantitatif analizine başarıyla uygulandı ve ardından iyi bir uyum olduğu bildirildi.

Keywords

Anjiyotensin II reseptör antagonistleri, hidroklorotiyazid, kandesartan sileksetil, kantitatif tablet analizi, üç değişkenli klasik en küçük kareler yöntemi

References

• 1. Burnier, M., Brunner, H.R. (1998). Angiotensin II receptor antagonists in hypertension. Kidney International, 45(68), 107-111. [CrossRef]
• 2. Gohlke, P., Jürgensen, T., von Kügelgen, S., Unger, T. (1999). Candesartan cilexetil: Development and preclinical studies. Drugs Today (Barc), 35(2), 105-115. [CrossRef]
• 3. Elmfeldt, D., George, M., Hübner, R., Olofsson, B. (1997). Candesartan cilexetil, a new generation angiotensin II antagonist, provides dose dependent antihypertensive effect. Journal of Human Hypertension, 11(2), 49-53. [CrossRef]
• 4. Ernst, M.E., Fravel, M.A. (2022). Thiazide and the thiazide-like diuretics: Review of hydrochlorothiazide, chlorthalidone, and indapamide. American Journal of Hypertension. 35(7), 573-586. [CrossRef]
• 5. Prajapati, S.T., Patel, P.K., Chauhan, V.B., Patel, C.N., Patel, M. (2011). Development and validation of the liquid chromatography-tandem mass spectrometry method for quantitative estimation of candesartan from human plasma. Pharmaceutical methods, 2 (2), 130-134. [CrossRef]
• 6. Hertzog, D.L., Finnegan J., McCafferty, J.F., Fang, X., Tyrrell, R.J., Reed, R.A. (2002). Development and validation of a stability-indicating HPLC method for the simultaneous determination of Losartan potassium, hydrochlorothiazide, and their degradation products. Journal of Pharmaceutical and Biomedical Analysis, 30, 747-760. [CrossRef]
• 7. González, L., Alonso, R.M., Jiménez, R.M. (2000). A high-performance liquid chromatographic method for screening angiotensin II receptor antagonists in human urine. Chromatographia, 52, 735-740. [CrossRef]
• 8. Üstündağ, Ö., Dinç, E. (2021). Continuous wavelet transforms and ultra-performance liquid chromatography applied to the simultaneous quantitative determination of candesartan cilexetil and hydrochlorothiazide in tablet. Monatshefte für Chemie - Chemical Monthly, 152, 1097-1106. [CrossRef]
• 9. Hillaert, S., Van den Bosshe, W. (2003). Simultaneous determination of hydrochlorothiazide and several angiotensin-II-receptor antagonists by capillary electrophoresis. Journal of Pharmaceutical and Biomedical Analysis, 31, 329-339. [CrossRef]
• 10. Zhang, M., Wei, F., Zhang, Y.F. (2006) Novel polymer monolith microextraction using a poly(methacrylic acid-ethylene glycol dimethacrylate) monolith and its application to simultaneous analysis of several angiotensin II receptor antagonists in human urine by capillary zone electrophoresis. Journal of Chromatography A, 1102, 294-301. [CrossRef]
• 11. Hillaert, S., De Beer, T.R., De Beer, J.O., Van den Bossche W. (2003). Optimization and validation of a micellar electrokinetic chromatographic method for the analysis of several angiotensin-II-receptor antagonists. Journal of Chromatography A, 984, 135-146. [CrossRef]
• 12. Lasure, A., Ansari, A., Kalshetti, M. (2020). UV spectrophotometric analysis and validation of acyclovir in solid dosage form. International Journal of Current Pharmaceutical Research,12 (2), 100-103. [CrossRef]
• 13. Dhole, S.M., Amnerkar, N.D., Khedekar, P.B. (2012). Comparison of UV spectrophotometry and high performance liquid chromatography methods for the determination of repaglinide in tablets. Pharmaceutical Methods, 3 (2), 68-72. [CrossRef]
• 14. Abdelwahab, N.S. (2016). Spectrophotometric methods for simultaneous determination of Carvedilol and Hydrochlorothiazide in combined dosage form. Arabian Journal of Chemistry, 9, 355-360. [CrossRef]
• 15. Lastra, O.C., Lemus, I.G., Sánchez, H.J., Pérez, R.F. (2003). Development and validation of an UV derivative spectrophotometric determination of Losartan potassium in tablets. Journal of Pharmaceutical and Biomedical Analysis, 33, 175-180. [CrossRef]
• 16. Tatar, S., Saglik, S. (2002) Comparison of UV- and second derivative-spectrophotometric and LC methods for the determination of valsartan in pharmaceutical formulation. Journal of Pharmaceutical and Biomedical Analysis, 30, 371-375. [CrossRef]
• 17. Redasani, V.K., Patel, P.R., Marathe, D.Y., Chaudhari, S.R., Shirkhedkar, A.A., Surana, S.J. (2018). A review on derivative UV-spectrophotometry analysis of drugs in pharmaceutical formulations and biological samples review. Journal of the Chilean Chemical Society, 63(3), 4126-4134. [CrossRef]
• 18. Mukthinuthalapati, M. A., Kumar, J. S. P. (2015). Simultaneous derivative spectrophotometric determination of candesartan cilexetil and hydrochlorothiazide. Pharmaceutical Methods, 6, 148-151.
• 19. Belal, T.S., Daabeesb, H.G., Abdel-Khalekb, M.M., Mahrousb, M.S., Khamisb, M.M. (2013). New simple spectrophotometric method for determination of the binary mixtures (atorvastatin calcium and ezetimibe; candesartan cilexetil and hydrochlorothiazide) in tablets. Journal of Pharmaceutical Analysis, 3(2), 118-126. [CrossRef]