Characterization of Impurities in Sulfasalazine

Zalipsky, J.J.; Patel, Dahyabhai M.; Reavey-Cantwell, Nelson H.

doi:10.1002/jps.2600670331

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…The fragmentation patterns of SAS obtained with both H 2 O and D 2 O solvent infusion methods were similar, however, some differences after the H/D exchange were also observed. Particularly the fragmentation using D 2 O solvent showed some different fragment ions, which seem to be related to the neutral losses of SAS[23,24]. SAS has a molecular ion at m/z 399.0772 and 403.0993 with H 2 O and D 2 O solvent, respectively, and this result matches well with the number of exchangeable protons (n = 3) in SAS.…”

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confidence: 52%

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Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry

et al. 2021

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Sulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc- (SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identification studies in the brain for SAS were quite limited. The aim of this study was to investigate the pharmacokinetics and metabolite identification of SAS and their distributions in mouse brain. Using in vivo brain exposure studies (neuro PK), the PK parameters of SAS was calculated for plasma as well as brain following intravenous and oral administration at 10 mg/kg and 50 mg/kg in mouse, respectively. In addition, in vivo metabolite identification (MetID) studies of SAS in plasma and brain were also conducted. The concentration of SAS in brain was much lower than that in plasma and only 1.26% of SAS was detected in mouse brain when compared to the SAS concentration in plasma (brain to plasma ratio (%): 1.26). In the MetID study, sulfapyridine (SP), hydroxy-sulfapyridine (SP-OH), and N-acetyl sulfapyridine (Ac-SP) were identified in plasma, whereas only SP and Ac-SP were identified as significant metabolites in brain. As a conclusion, our results suggest that the metabolites of SAS such as SP and Ac-SP might be responsible for the pharmacological effect in brain, not the SAS itself.

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confidence: 52%

“…To our best knowledge, this is the first report regarding SAS exposure and metabolite identification in mouse brain. Hydrogen/deuterium exchange (H/D exchange) for the product ion spectra by the electrospray ionization (ESI) was also performed to confirm the fragment pattern of SAS [23,24].…”

Section: Introductionmentioning

confidence: 99%

Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry

et al. 2021

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“…The most recent report on any analytical method for SSZ was published in 2011 where an HPLC method was developed for the quantification of SSZ along with mebeverine, mesalazine, and dispersible aspirin [24]. A thin-layer chromatography method was also reported for the characterization of process-related impurities in SSZ [25]. However, none of the reported study was carried out in accordance with the ICH guidelines that help in establishing the stability-indicating nature of the analytical method.…”

Section: Introductionmentioning

confidence: 99%

Degradation Study on Sulfasalazine and a Validated HPLC-UV Method for its Stability Testing

Saini

2014

Sci. Pharm.

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Sulfasalazine (SSZ) was subjected to degradation under the conditions of hydrolysis (acid, alkali, and water), oxidation (30% H2O2), dry heat, and photolysis (UV-VIS light) in accordance with the ICH guidelines. An RP-HPLC method was developed to study the degradation behavior. No degradation was noted under any condition except alkaline hydrolysis where SSZ was degraded to a single minor product. SSZ was optimally resolved from this product on an XTerra® RP18 column with a mobile phase composed of methanol and an ammonium acetate buffer (10 mM, pH 7.0) (48:52, v/v) delivered at a rate of 0.8 mL/min in an isocratic mode. The method was validated and found to be linear (r2=0.99945), precise (%RSD <2), robust, and accurate (94–102%) in the concentration range of 0.5–50 μg/mL of SSZ. The PDA analysis of the degraded sample revealed the SSZ peak purity to be 998.99 and the drug peak eluted with a resolution factor of >2 from the nearest resolving peak, indicating the method to be selectively stability-indicating for the drug analysis. The method was applied successfully for the stability testing of the commercially available SSZ tablets that were under varied ICH-prescribed conditions. An explanation for the unusual stability of the drug when exposed to acidic hydrolysis, despite the presence of the sulfonamide linkage, is also discussed.

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