Hydrolysis of Hydrochlorothiazide

Mollica, Joseph A.; Rehm, Carl R.; Smith, J. B.

doi:10.1002/jps.2600580531

Cited by 45 publications

(16 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[11][12][13][14] The literature also shows there are individual methods reported to study hydrolysis of hydrochlorothiazide and photolytic decomposition of hydrochlorothiazide in solution. 15,16 Few stability indicating assay methods were reported for hydrochlorothiazide and hydrochlorothiazide combination products.…”

Section: -5mentioning

confidence: 99%

See 1 more Smart Citation

LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation

Mahajan¹,

Thaker²,

Mohanraj³

2012

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

O objetivo do presente estudo foi separar, identificar e caracterizar os produtos de degradação de hidroclorotiazida, sob confições de estresse hidrolítico, oxidativo, fotolítico e térmico, conforme a diretriz Q1A (R2) da Conferência Internacional de Harmonização (ICH). A droga sofreu degradação sob estresse ácido, básico, neutro e oxidativo, enquanto permaneceu estável nas condições de estresse fotolítico e térmico. Dois produtos de degradação foram formados, os quais foram separados através de CLAE em coluna C18, usando um programa de eluição isocrática. Uma rota completa de fragmentação da droga foi estabelecida, primeiramente, com a ajuda de estudos de CL-EM/ EM. As amostras estressadas foram submetidas a estudos de CL-EM. Os dados dos espectros de massas foram empregados para caracterizar os produtos de degradação e atribuir estruturas. Os produtos de degradação foram identificados como 4-amino-6-cloro-1,3-benzenodissulfonamida e 6-cloro-2-oxi-3,4-diidro-2H-1,2,4-benzotiadiazina-7-sulfonamida-1,1-dióxido.The objective of the present investigation was to separate, identify and characterize the degradation products of hydrochlorothiazide under hydrolytic, oxidative, photolytic and thermal stress conditions as per the International Conference on Harmonization (ICH) guideline Q1A (R2). The drug degraded under acidic, basic, neutral and oxidative stress, while it was stable under photolytic and thermal stress conditions. Two degradation products were formed, which were separated by using HPLC on C18 column using isocratic elution program. A complete mass fragmentation pathway of the drug was first established with the help of LC-MS/MS studies. The stressed samples were subjected to LC-MS studies. The obtained mass spectral data were employed to characterize the degradation products and assign structures. The degradation products were identified as 4-amino-6-chloro-1,3-benzenedisulfonamide and 6-chloro-2-oxy-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.

show abstract

Section: -5mentioning

confidence: 99%

“…It was formed by loss of formaldehyde after hydrolysis. 15 This happened by initial ring opening to give compound III (Figure 4) which is stabilized by resonance (III, III A, III B). Water molecule then attacks compound III by 1,4 addition across the double bond, finally leading to loss of formaldehyde ( Figure 4).…”

Section: Accuracymentioning

confidence: 99%

LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation

Mahajan¹,

Thaker²,

Mohanraj³

2012

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…To further elucidate the proposed structure, the 1 H NMR of HCTZ in dimethyl sulfoxide-d 6 with added hydrochloric acid was acquired as a point of reference, using two-dimensional correlation spectroscopy (COSY), nuclear overhauser effect spectroscopy (NOESY), and total correlation spectroscopy (TOCSY) 1 H NMR. The COSY experiment shows that the methylene resonance at 4.71 ppm (d, 2H, C3) is directly correlated to the resonances at 7.97 ppm (t, 1H) and 8.02 ppm (br, 1H).…”

Section: Resultsmentioning

confidence: 99%

“…Chlorothiazide (CTZ) 5 and DSA are well-recognized process impurities that are formed during the synthesis of HCTZ. Furthermore, the degradation of HCTZ in aqueous solution has been previously studied by Mollica et al 1,2 and Yamana et al 3 HCTZ was found to degrade to DSA and formaldehyde via hydrolysis. Mollica et al studied the pH-rate pro®le of the hydrolysis of HCTZ at 608C and found a bellshaped curve plot of log K 1 versus pH with maximum at about pH 7.2 and minimum at pH 2.2 to 3.…”

Section: Introductionmentioning

confidence: 93%

Purification and identification of an impurity in bulk hydrochlorothiazide

Fang

Bibart

Mayr

et al. 2001

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…Different stability indicating HPLC methods have been reported in the determination of hydrochlorothiazide in pharmaceutical dosage forms (Lusina et al, 2005;Argekar, Sawant, 2000;Kanumula, Raman, 2000). Although degradation of HCTZ in aqueous solutions and its dependence on temperature and pH have been previously reported by Mollica, Rehm and Smith (1969), there is no kinetic assessment available for HCTZ and lactose interaction. In addition, no attention has been paid to the influence of pH on such interactions in drug molecules.…”

Section: Introductionmentioning

confidence: 99%

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

Ghaderi

Nemati

Siahi-Shadbad

et al. 2016

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of -hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs.Uniterms: Hydrochlorothiazide/lactose/Maillard reaction. Hydrochlorothiazide/lactose/interaction/ kinetic parameters. High Performance Liquid Chromatography (HPLC)/kinetic parameters study.

show abstract

Hydrolysis of Hydrochlorothiazide

Cited by 45 publications

References 13 publications

LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation

LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation

Purification and identification of an impurity in bulk hydrochlorothiazide

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

Contact Info

Product

Resources

About