High-Performance Liquid Chromatography and Liquid Chromatography/Mass Spectrometry Studies on Stress Degradation Behavior of Sulfapyridine and Development of a Validated, Specific, Stability-Indicating HPLC Assay Method.

The objective of the current investigation was to develop a simple, rapid, and stability-indicating high-performance liquid chromatography method and to study the degradation behavior of sulfapyridine (SP) under different International Conference on Harmonization (ICH)-recommended conditions. The chromatographic method was developed using C18 (250 × 4.6 mm, 5 µ) column, and mobile phase consisting of acetonitrile-0.1% formic acid (30:70 v/v) at ambient temperature, at a flow rate of 1 mL/min. The elution was monitored at 265 nm using a photodiode array detector. The developed method was subsequently validated as per ICH Q2 (R1) guidelines. The retention time of SP was observed as 4.56 min with the linearity range between 2 to 10 µg/mL. Limit of detection and limit of quantitation for SP were 0.115 and 0.35 µg/mL, respectively. Forced degradation studies were carried out on bulk samples of SP using prescribed acidic, basic, oxidative, thermal, and photolytic conditions. Extent of degradation in 0.1 M hydrochloric acid and under photolytic conditions was found to be 21.56% and 28.57%, respectively. The degradation products formed in stress conditions were identified by liquid chromatography-mass spectrometry (LC-MS). The utility of the method was verified by quantification of SP in different laboratory-made pharmaceutical preparations. The proposed method could be successfully used to quantify SP in different pharmaceutical dosage forms.

Pharmacokinetic evaluation of differential drug release formulations of rabeprazole in dogs.

Objectives: To develop novel dual release prototype capsule formulations of rabeprazole and evaluation of pharmacokinetic properties relative to the reference product (Aciphex®) in Beagle dogs. Methods: The dual release prototype formulations of rabeprazole were developed by preparing optimized mini-tablets core which was subsequently coated with barrier/enteric coating using standard excipients. Both novel prototype formulations were subjected for in vitro release and assay by HPLC-UV to assess long term stability. Single dose pharmacokinetic study used a single sequence three treatments crossover design. In Periods 1 and 2, four dogs received oral 20 mg dose of two prototype formulations. In Period 3, all dogs received a 20 mg oral dose of Aciphex® reference product. There was a 1-week washout time between two successive periods. A quantitative analysis of rabeprazole/sulfide metabolite in plasma samples was performed using a validated LC-MS/MS assay and PK parameters were estimated by non-compartmental analysis. Results: The stability of the prototype formulations was confirmed over a period of 24 months with an acceptable assay and dissolution data. One of the novel prototype formulations showed 70% oral bioavailability relative to the reference product. Despite a 30% reduced bioavailability, this showed 1 h delay in peak concentration, longer plasma residence time of rabeprazole (up to 12 h) and longer apparent elimination half-life. Conclusions: The use of a canine model has enabled the selection of a novel dual-release prototype formulation of rabeprazole for further clinical development.