Simultaneous Determination of Sulfasalazine and Its Metabolites Sulfapyridine and N-Acetylsulfapyridine in Human Serum by Ion-Pair High-Performance Liquid Chromatography Using a Polymer-Based Column

Buggé, Christopher J.L.; Gautam, Sushen R.; Parke, Leslie E.; Mason, James T.; Garcia, David B.

doi:10.1002/jps.2600791211

Cited by 15 publications

(4 citation statements)

References 10 publications

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“…In contrast, to the lower diclofenac bioavailability from the CD prodrug, sulfapyridine was completely absorbed from its prodrug as shown by the similar AUCs (59.4 µg.h/mL of the prodrug vs 61.8 µg.h/mL of the free compound). This reflects previous reports of high absorption of sulfapyridine following administration of sulfasalazine (Azad Khan and Truelove, 1980;Buggé et al, 1990). The difference in in vivo bioavailabilities of diclofenac and sulfapyridine from their prodrugs correlates with ex vivo studies which showed a much slower rate of release of diclofenac from diclofenac-β-cyclodextrin compared to the very fast release of sulfapyridine from sulfasalazine (Vieira et al, 2014).…”

Section: Discussionsupporting

confidence: 87%

Diclofenac-β-cyclodextrin for colonic drug targeting: In vivo performance in rats

Vieira

Serra

Veiga

et al. 2016

International Journal of Pharmaceutics

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The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a suspension containing the two prodrugs, diclofenac-β-cyclodextrin and sulfasalazine, while the control rats received a suspension containing the corresponding free drugs, sodium diclofenac and sulfapyridine. The rats were fasted overnight with free access to water before and throughout the first 12h of the study. Blood was collected from the tail vein at pre-determined time points and the plasma analyzed for the concentrations of diclofenac and sulfapyridine. Following the oral administration of the two prodrugs, a more extended absorption profile was observed and Cmax was achieved 10h post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3h, and that of sulfapyridine being 2.1h). In addition to a later tmax, conjugation of diclofenac to β-cyclodextrin also resulted in a reduced Cmax and a reduced AUC. The same tmax for diclofenac-β-cyclodextrin as for sulfasalazine confirms the colonic metabolism of diclofenac-β-cyclodextrin. This study shows the potential of this new cyclodextrin-based prodrug to target and release diclofenac specifically in the colon following oral administration.

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Section: Discussionsupporting

confidence: 87%

Diclofenac-β-cyclodextrin for colonic drug targeting: In vivo performance in rats

Vieira

Serra

Veiga

et al. 2016

International Journal of Pharmaceutics

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“…The International Conference on Harmonization (ICH), through its guidelines Q1A (R2) and Q1B [10, 11], requires the conduct of forced degradation studies to characterize all of the possible degradation products under varied conditions such as light, heat, humidity, acid/base hydrolysis, and oxidation in order to develop a stability-indicating assay method (SIAM) for the stability testing of a drug substance or product. An extensive literature search has revealed that several analytical methods were reported in the 1990s for the analysis of SSZ alone [12, 13], in the formulations [14], and in the presence of metabolites [15–21]. Peel et al, 1994 [22] and Coward et al, 1995 [23] had reported interference of SSZ with the HPLC assay of urine and 5-hydroxyindole-3-acetic acid, respectively.…”

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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“…Several analyses using high‐performance liquid chromatography (HPLC) have been reported for SLP, Ac‐SLP, 5‐ASA and acetyl 5‐ASA (8–11). However, the determination of drugs in serum and plasma using HPLC normally requires several sample preparation processes, such as filtration, deproteinization, extraction, centrifugation, and concentration.…”

Section: Introductionmentioning

confidence: 99%

Simple and simultaneous determination of sulphapyridine and acetylsulphapyridine in human serum by column-switching high-performance liquid chromatography

et al. 2002

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Simultaneous Determination of Sulfasalazine and Its Metabolites Sulfapyridine and N-Acetylsulfapyridine in Human Serum by Ion-Pair High-Performance Liquid Chromatography Using a Polymer-Based Column

Cited by 15 publications

References 10 publications

Diclofenac-β-cyclodextrin for colonic drug targeting: In vivo performance in rats

Diclofenac-β-cyclodextrin for colonic drug targeting: In vivo performance in rats

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

Simple and simultaneous determination of sulphapyridine and acetylsulphapyridine in human serum by column-switching high-performance liquid chromatography

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