- Stability-indicating assay for hydrochlorothiazide
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A stability-indicating method for determining hydrochlorothiazide in tablet formulations and in the bulk form is described. Hydrochlorothiazide is dissolved or extracted using methanol. An aliquot of the solution, containing sulfadiazine as an internal standard, is chromatographed on a 10-μm C18 column with an aqueous mobile phase containing 5% methanol as the modifier. The pH is adjusted to about 4.5 with acetic acid. The method gave accurate results for nine lots (four different suppliers) of tablets and two bulk drug lots (two different suppliers). The assay has a relative standard deviation of about 1%. The method can also be used as a test for impurities in hydrochlorothiazide. The data in this study indicate that the test should give accurate results for impurities between 0.1 and 5%.
- Daniels,Vanderwielen
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- Accelerated Forced Degradation of Pharmaceuticals in Levitated Microdroplet Reactors
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Forced degradation is a method of studying the stability of pharmaceuticals in order to design stable formulations and predict drug product shelf life. Traditional methods of reaction and analysis usually take multiple days, and include LC-UV and LC-MS product analysis. In this study, the reaction/analysis sequence was accelerated to be completed within minutes using Leidenfrost droplets as reactors (acceleration factor: 23–188) and nanoelectrospray ionization MS analysis. The Leidenfrost droplets underwent the same reactions as seen in traditional bulk solution experiments for three chemical degradations studied. This combined method of accelerated reaction and analysis has the potential to be extended to forced degradation of other pharmaceuticals and to drug formulations. Control of reaction rate and yield is achieved by manipulating droplet size, levitation time and whether or not make-up solvent is added. Evidence is provided that interfacial effects contribute to rate acceleration.
- Li, Yangjie,Liu, Yong,Gao, Hong,Helmy, Roy,Wuelfing, W. Peter,Welch, Christopher J.,Cooks, R. Graham
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- Effect of pharmaceutical excipients on the stability of trichlormethiazide tablets under humid conditions
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The stability of trichlormethiazide (TCM) and the drug in the nine products available on the market (the original tablet (B) and 8 generic tablets (G1-G8)) were investigated under humid conditions. TCM was non-hygroscopic and was not degraded under humid conditions. Drug degradation in aqueous ethanol was accelerated with increased water concentration, and the drug stability in buffer solution was improved with decreased pH. TCM decomposition was not detected in each unwrapped tablet at low relative humidity. However, rapid degradation was observed for products G1 and G2, while product B and G7 showed higher stability at high relative humidity. The stability of products G1 and G2 decreased with increasing humidity. The same results were observed for the tablets in press-through packages (PTP), but the degradation rate was much slower than tablets without PTP packages. These results suggested that the adsorbed moisture by excipients cause TCM degradation. Various pharmaceutical excipients are added to TCM tablets and these vary between different pharmaceutical companies. Intact drug and pharmaceutical excipients, including lactose, microcrystalline cellulose, corn starch, hydroxypropylcellulose (HPC), low substituted HPC (L-HPC), calcium stearate, and light anhydrous silicic acid, were mixed, and the sample mixtures were stored in humid conditions. It was found that the TCM content decreased significantly in a binary mixture of TCM/HPC 1:1.
- Teraoka, Reiko,Matsushima, Yuki,Sugimoto, Isao,Inoue, Kana,Morita, Shin-Ya,Kitagawa, Shuji
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- LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation
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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.
- Mahajan, Anand Avinash,Thaker, Anil Keshavlal,Mohanraj, Krishnapriya
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experimental part
p. 445 - 452
(2012/05/20)
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- Photolytic decomposition of hydrochlorothiazide
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Hydrochlorothiazide decomposes upon irradiation with near-UV light (λ > 310 nm) both in methanol and aqueous solutions. In the photolysis the chlorine substituent is removed to be replaced by either -H or -OR from the solvent ROH. Hydrolysis of the thiadiazine ring is superimposed upon the dechlorination. The presence of oxygen inhibits the decomposition. The mechanism of the photolysis is suggested to involve cation radical formation which facilitates the hydrolysis step. 5-Chloro-2,4-disulphonamido-aniline, the normal hydrolysis product from hydrochlorothiazide, is also susceptible to photolytic dechlorination by a similar mechanism.
- Tamat,Moore
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p. 180 - 183
(2007/10/02)
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