首页|Development and validation of HPLC-DAD and LC-(ESI)/MS methods for the determination of sulfasalazine, mesalazine and hydrocortisone 21-ace- tate in tablets and rectal suppositories: In vitro and ex vivo permeability studies

Development and validation of HPLC-DAD and LC-(ESI)/MS methods for the determination of sulfasalazine, mesalazine and hydrocortisone 21-ace- tate in tablets and rectal suppositories: In vitro and ex vivo permeability studies

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  • NSTL
  • Elsevier
Controlled-release tablets and rectal suppositories of sulfasalazine (SLF) and hydrocortisone 21-acetate (HA) were prepared as recommended dosage forms for the treatment of acute episodes of ulcerative colitis, in patients who do not respond to monotherapy.A High-Performance Liquid Chromatography (HPLC) Diode-array method with a gradient elution mobile phase was developed to evaluate the production quality of both formulations (assay and dissolution profiles in gastric and intestinal fluids). Method's validation was carried out providing good linearity (r > 0.9995), precision (RSD < 1.53%), recovery (96.9% - 103.7%) and limits of detection (LODSLF = 12 ng/mL, LODHA = 15 ng/ mL). Experimental design and Plackett-Burman methodology was constructed to study the robustness of the analysis. In all composite substrates, a freezing lipid precipitation approach was used as purification step. The method was optimized by applying Central Composite design mode. The in-vitro/ex-vivo permeability studies of both formulations were evaluated by a Liquid ChromatographyElectron Spray Ionization Mass Spectrometry (LC-ESI/MS) +/- mode. The analysis of sulfamethazine (internal standard, SLM, m/z 279), HA (m/z 449, [M + HCOO]-), SLF (m/z 399) and its active metabolite mesalazine (MSL, m/z 154) was performed using a C18 column and gradient elution. The validation of the method met the requirements of the International Council for Harmonization (ICH) (r > 0.9997, RSD <= 4.62%, Recovery > 95%, LODSLF = 1.28 ng/mL, LODHA = 1.07 ng/mL, LODMSL = 3.16 ng/mL). Based on the results, important conclusions were drawn concerning the role of excipients and SLF metabolism.

SulfasalazineHydrocortisone 21-acetateChromatographic separationsExperimental designPermeability studiesFreezing-out techniqueLIQUID-CHROMATOGRAPHIC METHODCLINICAL PHARMACOKINETICSMAJOR METABOLITESACETATEBIOAVAILABILITYSULPHASALAZINETRANSPORTPLASMA

Tsamis, Vasileios、Tsanaktsidou, Eleni、Karavasili, Christina、Zacharis, Constantinos K.、Bouropoulos, Nikolaos、Fatouros, Dimitrios G.、Markopoulou, Catherine K.

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Aristotle Univ Thessaloniki

Univ Patras

2022

10.1016/j.jchromb.2022.123246

Journal of chromatography

Journal of chromatography

ISSN：1570-0232
年,卷(期)：2022.1198
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