ZERO-ORDER AND FIRST-DERIVATIVE SPECTROPHOTOMETRY FOR THE DETERMINATION OF SPIRONOLACTONE IN PHARMACEUTICAL TABLETS

Öz

Objective: Spironolactone, a potassium-sparing diuretic drug on the WHO's Essential Medicines List, is primarily used to treat fluid retention resulting from heart failure, kidney disease, and liver scarring. In this research article, zero-order, and first-derivative spectrophotometric approaches were applied to the quantity of spironolactone in pharmaceutical tablet formulation without any separation procedure. Material and Method: Spironolactone compound was obtained from Sigma-Aldrich (Steinheim, Germany). As a solvent methanol (J.T. Baker, Netherlands, HPLC grade) was used for UV-visible spectrophotometric assays. In the implementation of the zero-order and first-derivative approaches, the quantification of Spironolactone was carried out using UV spectrophotometric measurements in the 200-300 nm wavelength range (with a 2 nm increment) and 1 cm quartz cells. These approaches were tested by analyzing spironolactone in independent test samples and spiked samples. The tablet analyses of spironolactone were performed on ALDACTONE®-A 25 mg Tablet supplied by Aris Ali Raif Pharmaceuticals Industry, Başakşehir, İstanbul, Türkiye. Result and Discussion: The analysis of spironolactone was conducted using zero-order values measured at 239 nm and first-derivative values measured at 250.4 nm (n=3). The calibration graphs created at these wavelengths showed linearity within the 6.0 to 20.0 µg/ml concentration range, with correlation coefficients of r = 0.9996 for the zero-order method and r = 0.9997 for the first-order derivative method. The validity of the methods was proved by analyzing spironolactone in independent test samples and spiked samples. These methods were then applied to the quantitation of spironolactone in commercial tablets and a good agreement was reported between label claim assay results.

Anahtar Kelimeler

• Antihyypertensive drug
• determination of spironolactone
• first derivative spectrophotometry
• tablet analysis
• zero-order spectrophotometry

FARMASÖTİK TABLETLERDEKİ SPİRONOLAKTONUN TAYİNİ İÇİN SIFIR DERECEDEN VE BİRİNCİ TÜREV SPEKTROFOTOMETRİ

Öz

Amaç: WHO'nun Temel İlaçlar Listesi'nde yer alan potasyum tutucu bir diüretik ilaç olan spironolakton, öncelikli olarak kalp yetmezliği, böbrek hastalığı ve karaciğer skarlaşmasından kaynaklanan sıvı tutulumunu tedavi etmek için kullanılır. Bu araştırma makalesinde, herhangi bir ayırma prosedürü olmaksızın farmasötik tablet formülasyonundaki spironolakton miktarına sıfırıncı mertebeden ve birinci türev spektrofotometrik yaklaşımlar uygulandı. Gereç ve Yöntem: Spironolakton bileşiği Sigma-Aldrich'ten (Steinheim, Almanya) elde edildi. Çözücü olarak metanol (J.T. Baker, Hollanda, HPLC sınıfı) UV-görünür spektrofotometrik analizler için kullanıldı. Sıfırıncı mertebe ve birinci türev yaklaşımlarının uygulanmasında, Spironolaktonun kantifikasyonu 200-300 nm dalga boyu aralığında (2 nm artışla) ve 1 cm kuvars hücrelerde UV spektrofotometrik ölçümler kullanılarak gerçekleştirildi. Bu yaklaşımlar, spironolaktonun bağımsız test örneklerinde ve spike edilmiş örneklerde analiz edilmesiyle test edildi. Spironolaktonun tablet analizleri, Aris Ali Raif İlaç Sanayi, Başakşehir, İstanbul, Türkiye tarafından tedarik edilen ALDACTONE®-A 25 mg Tablet üzerinde gerçekleştirildi. Sonuç ve Tartışma: Spironolakton analizi, 239 nm'de ölçülen sıfırıncı mertebeden değerler ve 250,4 nm'de ölçülen birinci türev değerleri kullanılarak gerçekleştirildi (n=3). Bu dalga boylarında oluşturulan kalibrasyon grafikleri, sıfırıncı mertebeden yöntem için r = 0,9996 ve birinci mertebeden türev yöntemi için r = 0,9997 korelasyon katsayılarıyla 6,0 ila 20,0 µg/ml konsantrasyon aralığında doğrusallık gösterdi. Yöntemlerin geçerliliği, bağımsız test örneklerinde ve güçlendirilmiş örneklerde spironolaktonun analiz edilmesiyle kanıtlandı. Daha sonra bu yöntemler ticari tabletlerdeki spironolaktonun kantifikasyonuna uygulandı ve etiket iddiası deney sonuçları arasında iyi bir uyum bildirildi.

Anahtar Kelimeler

• Antihipertansif ilaç
• birinci türev spektrofotometri
• sıfırıncı mertebe spektrofotometri
• spironolakton tayini
• tablet analizi

Kaynakça

1. 1. Zhou, D., Xi, B., Zhao, M., Wang, L., Veeranki, S.P. (2018). Uncontrolled hypertension increases risk of all-cause and cardiovascular disease mortality in US adults: The NHANES III Linked mortality study. Scientific Reports, 8, 9418. [CrossRef]
2. 2. De Bhailis, Á.M., Kalra, P.A. (2022). Hypertension and the kidneys. British Journal of Hospital Medicine (Lond), 83, 5, 1-11. [CrossRef]
3. 3. Mills, K.T., Stefanescu, A., He, J. (2020). The global epidemiology of hypertension. Nature Reviews Nephrology 16, 223-237. [CrossRef]
4. 4. Tsao, C.W., Aday, A.W., Almarzooq, Z.I., Anderson, C.A.M., Arora, P., Avery, C.L. (2023). Heart disease and stroke statistics-2023 update: A report from the American Heart Association. Circulation, 147, e93-e621. [CrossRef]
5. 5. Roth, G.A., Mensah, G.A., Johnson, C.O., Addolorato, G., Ammirati, E., Baddour, L.M., Barengo, N.C., Beaton, A.Z., Benjamin, E.J., Benziger, C.P., Bonny, A., Brauer, M., Brodmann, M., Cahill, T.J., Carapetis, J., Catapano, A.L., Chugh, S.S., Cooper, L.T., Coresh, J., Criqui, M., DeCleene, N., Eagle, K.A., Bell, S.E., Feigin, V.L., Sola, J.F., Fowkes, G., Gakidou, E., Grundy, S.M., He, F.J., Howard, G., Hu, F., Inker, L., Karthikeyan, G., Kassebaum, N., Koroshetz, W., Lavie, C., Jones, D.,L., Lu, H.S., Mirijello, A., Temesgen, A.M., Mokdad, A., Moran, A.E., Muntner, P., Narula, J., Neal, B., Ntsekhe, M., Oliveira, G.M., Otto, C., Owolabi, M., Pratt, M., Rajagopalan, S., Reitsma, M., Ribeiro, A.L.P, Rigotti, N., Rodgers, A., Sable, C., Shakil, S., Hahnle, K.S., Stark, B., Sundström, J., Timpel, P, Tleyjeh, I.M., Valgimigli, M., Vos, T., Whelton, P.K., Yacoub, M., Zuhlke, L., Murray, C., Fuste, V. (2020). Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. Journal of the American College of Cardiology, 76, 2982-3021. [CrossRef]
6. 6. Wright, J.M., Musini, V.M., Gill, R. (2018). First-line drugs for hypertension. Cochrane Database of Systematic Reviews 4, CD001841. [CrossRef]
7. 7. Carey, R.M., Moran, A.E., Whelton, P.K. (2022). Treatment of hypertension: A review. Jama, 328, 1849-1861. [CrossRef]
8. 8. Sandall, J.M., Millership, J.S., Collier, P.S., McElnay, J.C. (2006). Development and validation of an HPLC method for the determination of spironolactone and its metabolites in pediatric plasma samples. Journal of Chromatography B, 839 (1-2) 36-44. [CrossRef]

9. 9. World Health Organization model list of essential medicines: 21st list 2019. Cenevre: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. https://iris.who.int/handle/10665/325771.
10. 10. McMullen, G.R., Van Herle, A.J. (1993). Hirsutism and the effectiveness of spironolactone in its management. Journal of Endocrinological Investigation, 16(11), 925-32. [CrossRef]
11. 11. Doggrell, S.A., Brown, L. (2001). The spironolactone renaissance. Expert Opinion on Investigational Drugs, 10(5), 943-54. [CrossRef]
12. 12. Burinkul, S., Panyakhamlerd, K., Suwan, A., Tuntiviriyapun, P., Wainipitapong, S. (2021). Anti-androgenic effects comparison between cyproterone acetate and spironolactone in transgender women: A randomized controlled trial. The Journal of Sexual Medicine, 18(7), 1299-1307. [CrossRef]
13. 13. Ma, Y., Peng, Y., Xu, Y., Yang, G., Hu, Q. (2010). Determination of atenolol, rosuvastatin, spironolactone, glibenclamide and naproxen in blood by rapid analysis liquid chromatography. Asian Journal of Chemistry, 22(2), 1136-1140.
14. 14. Vlase, L., Imre, S., Muntean, D., Achim, M., Muntean, D.L. (2011). Determination of spironolactone and canrenone in human plasma by high-performance liquid chromatography with mass spectrometry detection. Croatica Chemica Acta, 84(3), 361-366. [CrossRef]
15. 15. Ram, V.R., Dave, P.N., Joshi, H.S. (2012). Development and validation of a stability-indicating HPLC assay method for simultaneous determination of spironolactone and furosemide in tablet formulation. Journal of Chromatographic Science, 50(8), 721-726. [CrossRef]
16. 16. Walash, M., El-Enany, N., Eid, M., Fathy, M. (2013). Simultaneous determination of metolazone and spironolactone in raw materials, combined tablets and human urine by high performance liquid chromatography. Analytical Methods, 5(20), 5644-5656. [CrossRef]
17. 17. Lee, J.H., An., T.G., Kim, S.J., Shim, W.S., Lee, K.T. (2015). Development of liquid chromatography tandem mass spectrometry method for determination of spironolactone in human plasma: application to a bioequivalence study of Daewon Spiracton tablet® (spironolactone 50 mg). Journal of Pharmaceutical Investigation, 45(6), 601-609. [CrossRef]
18. 18. Al-Ghamdi, A.H., Al-Ghamdi, A.F., Al-Omar, M.A. (2008). Electrochemical studies and square-wave adsorptive stripping voltammetry of spironolactone drug. Analytical Letters, 41(1), 90-103. [CrossRef]
19. 19. El-Shahawi, M.S., Bashammakh, A.S., Al-Sibaai, A.A., Bahaidarah, E.A. (2013). Analysis of spironolactone residues in industrial wastewater and in drug formulations by cathodic stripping voltammetry. Journal of Pharmaceutical Analysis, 3(2), 137-143. [CrossRef]
20. 20. Smajdor, J., Piech, R., Paczosa-Bator, B. (2018). Spironolactone voltammetric determination on renewable amalgam film electrode. Steroids, 130, 1-6. [CrossRef]
21. 21. Dinç, E., Üstündağ, Ö. (2003). Spectophotometric quantitative resolution of hydrochlorothiazide and spironolactone in tablets by chemometric analysis methods. Il Farmaco, 58(11), 1151-1161. [CrossRef]
22. 22. Emam, A.A., Abdelaleem. E.A., Naguib, I.A., Abdallah, F.F., Ali, N.W. (2018). Successive ratio subtraction as a novel manipulation of ratio spectra for quantitative determination of a mixture of furosemide, spironolactone, and canrenone. Spectrochimica Acta Part A, 192, 427-436. [CrossRef]
23. 23. Patel, H., Solanki, S. (2012). Development and validation of spectrophotometric methods for simultaneous estimation of furosemide and spironolactone in combined tablet dosage form. International Journal of Pharmacy and Pharmaceutical Sciences, 4(4), 383-386.
24. 24. Golher, H.K., Kapse, K., Singh, S.K. (2011). Simultaneous spectrophotometric estimation of torsemide and spironolactone in tablet dosage form. International Journal of Pharmtech Research, 2(4), 2246-2250.
25. 25. Hegazy, M.A., Metwaly, F.H., Abdelkawy, M., Abdelwahab, N.S. (2010). Spectrophotometric and chemometric determination of hydrochlorothiazide and spironolactone in binary mixture in the presence of their impurities and degradants. Drug Testing and Analysis, 2(5), 243-251. [CrossRef]
26. 26. Dinç, E., Üstündağ, Ö. (2002). Chemometric resolution of a mixture containing hydrochlorothiazide and amiloride by absorption and derivative spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 29(1-2), 371-379. [CrossRef]