Simple and Rapid Determination of Diuretics by Luminescent Method

Iuna Tsyrulneva, Olga Zaporozhets

Chemistry Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine..

DOI: 10.4236/pp.2013.47075                

Abstract

Diuretics are drugs widely used in treatment of heart failure and hypertension and as doping agents in sports. Wrong prescription and excessive abuse can lead to negative side effects. Despite the effectiveness of methods usually used for the determination of diuretics (gas or liquid chromatography, capillary electrophoresis), they do not always provide necessary sensitivity. Moreover, sample preparation increases time of analysis. A rapid and sensitive luminescent method for determination of 5 diuretics (amiloride, bendroflumethiazide, bumetanide, furosemide, triamterene) in aqueous solutions and amiloride and triamterene in human urine is described. Intrinsic luminescent properties of protolytic forms of diuretics were studied in order to provide highly sensitive analysis. Investigation of interfering influence of diuretics was carried out to provide selective determination of triamterene, bumetanide and furosemide in aqueous mixtures of diuretics. Influence of urine at luminescent properties of diuretics was studied. The possibility of determination of triamterene and amiloride in human urine as individual substances and in mixture was proved. Simple and rapid technique for their determination in human urine was elaborated. The techniques elaborated for determination of triamterene in presence of other diuretics and furosemide in presence of commensurate amount of bumetanide allow enhancing specifity of analysis. Sufficient selectivity and sensitivity were reached in determination of amiloride and triamterene in human urine. The reduction of time of analysis due to avoiding sample preparation merits the techniques proposed.

Keywords

Furosemide; Bumetanide; Amiloride; Triamterene; Thiazides; Separation; Luminescence; Human Urine

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. Ventura and J. Segura, “Detection of Diuretic Agents in Doping Control,” Journal of Chromatography B: Biomedical Sciences and Applications, Vol. 687, No. 1, 1996, pp. 127-144. http://dx.doi.org/10.1016/S0378-4347(96)00279-4
[2]	A. Morganti, “Should a Diuretic Always Be the First Choice in Patients with Essential Hypertension? The Case for No,” Journal of the American Society of Nephrology, Vol. 16, No. 3, 2005, pp. 70-73. http://dx.doi.org/10.1681/ASN.2004110964
[3]	WADA, “The World Anti-Doping Code—The 2009 Prohibited List: International Standard,” World Anti-Doping Agency, Montreal, 2009.
[4]	WADA, “Minimum Required Performance Limits for Detection of Prohibited Substances (Technical Document TD2009MRPL),” World Anti-Doping Agency, Montreal, 2009.
[5]	C. Brunelli, C. Bicchi, A. Di Stilo, A. Salomone and M. Vincenti, “High-Speed Gas Chromatography in Doping Control: Fast-GC and Fast-GC/MS Determination of β-Adrenoceptor Ligands and Diuretics,” Journal of Separation Science, Vol. 29, No. 18, 2006, pp. 2765-2771. http://dx.doi.org/10.1002/jssc.200500387
[6]	R. Ventura, M. Roig, N. Monfort, P. Saez, R. Berges and J. Segura, “High-Throughput and Sensitive Screening by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry of Diuretics and Other Doping Agents,” European Journal of Mass Spectrometry, Vol. 14, No. 3, 2008, pp. 191-200. http://dx.doi.org/10.1255/ejms.920
[7]	M. Mazzarino, X. de la Torre and F. Botrè, “A Screening Method for the Simultaneous Detection of Glucocorticoids, Diuretics, Stimulants, Anti-Estrogens, Beta-Adrenergic Drugs and Anabolic Steroids in Human Urine by LC-ESI-MS/MS,” Analytical and Bioanalytical Chemistry, Vol. 392, No. 4, 2008, pp. 681-698. http://dx.doi.org/10.1007/s00216-008-2292-5
[8]	O. J. Pozo, P. Van Eenoo, K. Deventer and F. T. Delbeke, “Development and Validation of a Qualitative Screening Method for the Detection of Exogenous Anabolic Steroids in Urine by Liquid Chromatography-Tandem Mass Spectrometry,” Analytical and Bioanalytical Chemistry, Vol. 389, No. 4, 2007, pp. 1209-1224. http://dx.doi.org/10.1007/s00216-007-1530-6
[9]	K. Deventer, O. J. Pozo, P. Van Eenoo and F. T. Delbeke, “Qualitative Detection of Diuretics and Acidic Metabolites of Other Doping Agents in Human Urine by High-Performance Liquid Chromatography-Tandem Mass Spectrometry. Comparison between Liquid-Liquid Extraction and Direct Injection,” Journal of Chromatography A, Vol. 1216, No. 31, 2009, pp. 5819-5827. http://dx.doi.org/10.1016/j.chroma.2009.06.003
[10]	V. Morra, P. Davit and P. Capra, “Fast Gas Chromatographic/Mass Spectrometric Determination of Diuretics and Masking Agents in Human Urine. Development and Validation of a Productive Screening Protocol for Antidoping Analysis,” Journal of Chromatography A, Vol. 1135, No. 2, 2006, pp. 219-229. http://dx.doi.org/10.1016/j.chroma.2006.09.034
[11]	L. Amendola, C. Colamonici, M. Mazzarino and F. Botrè, “Rapid Determination of Diuretics in Human Urine by Gas Chromatography-Mass Spectrometry Following Microwave Assisted Derivatization,” Analytica Chimica Acta, Vol. 475, No. 1-2, 2003, pp. 125-136. http://dx.doi.org/10.1016/S0003-2670(02)01223-0
[12]	Yi.-L. Tseng, M.-H. Shieh, Ch.-Ts. Lin and F.-H. Kuo, “Detection of Diuretics in Urine during Sports Events in Taiwan,” Tzu Chi Medical Journal, Vol. 16, No. 2, 2004, pp. 69-77.
[13]	O. Zaporozhets, I. Tsyrulneva and M. Ischenko, “Determination of 8 Diuretics and Probenecid in Human Urine by Gas Chromatography-Mass Spectrometry: Confirmation Procedure,” American Journal of Analytical Chemistry, Vol. 3, No. 4, 2012, pp. 320-327. http://dx.doi.org/10.4236/ajac.2012.34044
[14]	J. A. M. Pulgarin, A. A. Molina and P. F. Lopez, “Direct Analysis of Amiloride and Triamterene Mixtures by Fluorescence Spectrometry Using Partial-Least Squares Calibration,” Analytica Chimica Acta, Vol. 449, No. 1-2, 2001, pp. 179-187. http://dx.doi.org/10.1016/S0003-2670(01)01356-3
[15]	J. A .M. Pulgarin, A. A. Molina and P. F. Lopez, “Simultaneous Direct Determination of Amiloride and Triamterene in Urine Using Isopotential Fluorometry,” Analytical Biochemistry, Vol. 292, No. 1, 2001, pp. 59-68. http://dx.doi.org/10.1006/abio.2001.5064
[16]	P. C. Ioannou, N. V. Rusakova, D. A. Andrikopoulou, K. M. Glynou and G. M. Tzompanakia, “Spectrofluorimetric Determination of Anthranilic Acid Derivatives Based on Terbium Sensitized Fluorescence,” Analyst, Vol. 123, No. 12, 1998, pp. 2839-2843. http://dx.doi.org/10.1039/a806093b
[17]	C. M. Peralta, L. P. Fernández and A. N. Masi, “Solid Phase Extraction Using Nylon Membranes with Fluorescence Detection as a Fast and Sensitive Method for Amiloride and Furosemide Determination in Urine Samples,” Microchemical Journal, Vol. 98, No. 1, 2011, pp. 39-43. http://dx.doi.org/10.1016/j.microc.2010.10.009
[18]	G. A. Ibanez, G. M. Escandar, A. E. Mansilla and A. M. de la Pena, “Determination of Triamterene in Pharmaceutical Formulations and of Triamterene and Its Main Metabolite Hydroxytriamterene Sulfate in Urine Using Solid-Phase and Aqueous Solution Luminescence,” Analytica Chimica Acta, Vol. 538, No. 1-2, 2005, pp. 77-84. http://dx.doi.org/10.1016/j.aca.2005.02.001
[19]	B. Song, A. K. Galande, K. Kodukula, W. H. Moos and S. M. Miller, “Evaluation of the PKa Values and Ionization Sequence of Bumetanide Using 1H and 13C NMR and UV Spectroscopy,” Drug Development Research, Vol. 72, No. 5, 2011, pp. 416-426. http://dx.doi.org/10.1002/ddr.20443
[20]	M. J. P. Leiner, M. R. Hubmann and O. S. Wolfbeis, “The Total Fluorescence of Human Urine,” Analytica Chimica Acta, Vol. 198, 1987, pp. 13-23. http://dx.doi.org/10.1016/S0003-2670(00)85002-3