Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Determination of Hydrochlorothiazide and Two Major Degradation Products by Stability Indicating High Performance Liquid Chromatography

Author(s): Larissa Sakis Bernardi, Pedro Nicolau Severino Júnior, Isabela Fanelli Barreto Biscaia , Maximiliano da Silva Sangoi, Vitor Todeschini, Cassiana Mendes, Marcos Antônio Segatto Silva and Paulo Renato Oliveira*

Volume 16, Issue 2, 2020

Page: [176 - 180] Pages: 5

DOI: 10.2174/1573412914666181017151551

Price: $65

Abstract

Background: Hydrochlorothiazide (HCTZ) is a thiazide diuretic which comprises two sulfonamide groups. The literature is not clear regarding the identification of the chromatographic peaks of its two major related substances: chlorothiazide and 4-amino-6-chloro-1,3-benzenedisulfonamide (DSA).

Methods: In the present study, a simple, sensitive, and selective HPLC method was developed and validated for the assay of HCTZ, Chlorothiazide and DSA. The method was carried out on a C18 column, maintained at 40ºC. The mobile phase was composed of monobasic potassium phosphate buffer 0.02M pH 3.0/acetonitrile/methanol (82:9:9, v/v/v), run at a flow rate of 1.0 mL/min, and UV detection at 270 nm.

Results: All related compounds including processing impurities and degradants from stressed samples were well separated from each other. The performance of this method was validated in accordance to the ICH guidelines and included specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness.

Conclusion: Based on the results, the HCTZ degradation pathway was proposed and the validated HPLC method was successfully applied to the quantitative analysis of HCTZ in pharmaceutical formulations, contributing to improve quality control, to assure therapeutic efficacy and to clarify the literature.

Keywords: Hydrochlorothiazide, chlorothiazide, high-performance liquid chromatography, validation, related substances, impurities.

Graphical Abstract

[1]
Kogawa, A.C.; Salgado, H.R.N. Impurities and forced degradation studies: A review. Curr. Pharm. Anal., 2016, 12, 18-24.
[2]
Holm, R.; Elder, D.P. Analytical advances in pharmaceutical impurity profiling. Eur. J. Pharm. Sci., 2016, 87(118), 1-89.
[3]
Luo, Z.; Liu, A.; Liu, Y.; Wang, G.; Chen, X.; Wang, H.; Li, M.; Zhang, H.; Qiu, Y.; Zhai, H. Development of a stability- indicating hplc method for simultaneous determination of ten related substances in vonoprazan fumarate drug substance. J. Pharm. Biomed. Anal., 2018, 149, 133-142.
[4]
Jain, D.; Basniwal, P.K. Forced degradation and impurity profiling: recent trends in analytical perspectives. J. Pharm. Biomed. Anal., 2013, 86(13), 11-35.
[5]
Blessy, M.; Patel, R.D.; Prajapati, P.N.; Agrawal, Y.K. Development of forced degradation and stability indicating studies of drugs - a review. J. Pharm. Anal., 2014, 4(3), 159-165.
[6]
Messerli, F.H.; Makani, H.; Benjo, A.; Romero, J.; Alviar, C.; Bangalore, S. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials. J. Am. Coll. Cardiol., 2011, 57(5), 590-600.
[7]
Pires, M.A.S.; Dos Santos, R.A.S.; Sinisterra, R.D. Pharmaceutical composition of hydrochlorothiazide: β-Cyclodextrin: preparation by three different methods, physico-chemical characterization and in vivo diuretic activity evaluation. Molecules, 2011, 16(6), 4482-4499.
[8]
Santoveña, A.; Hernández-Paiz, Z.; Fariña, J.B. Design of a pediatric oral formulation with a low proportion of hydrochlorothiazide. Int. J. Pharm., 2012, 423(2), 360-364.
[9]
Fang, X.; Bibart, R.T.; Mayr, S.; Yin, W.; Harmon, P.A.; Mccafferty, J.F.; Tyrrell, R.J.; Reed, R.A. Purification and identifcation of an impurity in bulk hydrochlorothiazide. J. Pharm. Sci., 2001, 90(11), 1800-1809.
[10]
Tagliari, M.P.; Stulzer, H.K.; Murakami, F.S.; Kuminek, G.; Valente, B.; Oliveira, P.R.; Segatto Silva, M.A. Development and validation of a stability-indicating lc method to quantify hydrochlorothiazide in oral suspension for pediatric use. Chromatographia, 2008, 67(7-8), 647-652.
[11]
Sangoi, M.S.; Wrasse-Sangoi, M.; Oliveira, P.R.; Rolim, C.M.B.; Steppe, M. Simultaneous determination of aliskiren and hydrochlorothiazide from their pharmaceutical preparations using a validated stability-indicating MEKC method. J. Sep. Sci., 2011, 34(15), 1859-1866.
[12]
Mollica, J.A.; Rehm, C.R.; Smith, J.B. Hydrolysis of Hydrochlorothiazide. J. Pharm. Sci., 1969, 58(5), 635-636.
[13]
Lusina, M.; Cindrić, T.; Tomaić, J.; Peko, M.; Pozaić, L.; Musulin, N. Stability study of losartan/hydrochlorothiazide tablets. Int. J. Pharm., 2005, 291(1-2), 127-137.
[14]
Daniels, S.L.; Vanderwielen, A.J. Stability‐indicating Assay for Hydrochlorothiazide. J. Pharm. Sci., 1981, 70(2), 211-215.
[15]
Thomas, B.R.; Fang, X.G.; Chen, X.; Tyrrell, R.J.; Ghodbane, S. Validated micellar electrokinetic capillary chromatography method for quality control of the drug substances hydrochlorothiazide and chlorothiazide. J. Chromatogr. B., 1994, 657(2), 383-394.
[16]
Mahajan, A.A.; Thaker, A.K.; Mohanraj, K.LC. LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation. J. Braz. Chem. Soc., 2012, 23(3), 445-452.
[17]
Urupina, D.; Al-Bazi, S. Stability-indicating method development and validation for the assay of hydrochlorothiazide and determination of impurities/ degradants in hydrochlorothiazide raw material and tablets using reverse-phase liquid chromatography. Austin J. Anal. Pharm. Chem., 2016, 3(3), 1-7.
[18]
International Conference on Harmonisation Guideline on Photostability Testing of New Drug Substances and Products, Q1B; 1996.
[19]
International Conference on Harmonisation Guideline on Stability Testing of New Drug Substances and Products, Q1A(R2); 2003.
[20]
International Conference on Harmonisation Guideline on Validation of Analytical Procedures: Text and Methodology, Q2(R1); 2005.
[21]
International Conference on Harmonisation Guideline on Impurities in New Drug Products, Q3B(R2); 2006.
[22]
Hertzog, D.L.; McCafferty, J.F.; Fang, X.; Tyrrell, R.J.; Reed, R.A. Development and validation of a stability-indicating hplc method for the simultaneous determination of losartan potassium, hydrochlorothiazide, and their degradation products. J. Pharm. Biomed. Anal., 2002, 30(3), 747-760.
[23]
Deventer, K.; Baele, G.; Van Eenoo, P.; Pozo, O.J.; Delbeke, F.T. Stability of selected chlorinated thiazide diuretics. J. Pharm. Biomed. Anal., 2009, 49(2), 519-524.
[24]
Razak, O.A. Electrochemical study of hydrochlorothiazide and its determination in urine and tablets. J. Pharm. Biomed. Anal., 2004, 34(2), 433-440.
[25]
Mendes, C.; Buttchevitz, A.; Kruger, J.H.; Kratz, J.M.; Simões, C.M.O.; De Oliveira Benedet, P.; Oliveira, P.R.; Silva, M.A.S. Inclusion complexes of hydrochlorothiazide and β-cyclodextrin: physicochemical characteristics, in vitro and in vivo studies. Eur. J. Pharm. Sci., 2016, 83, 71-78.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy