Abstract
Multifaceted comparative analytical methods for trelagliptin (TRL) were investigated, applied to ZAFATEK tablets and HPLC-UV was selected for a degradation kinetic study. UPLC-MS/MS (Method I), UPLC-UV (Method II), HPLC-UV (Method III), UHPLC-UV (Method IV) and direct UV (Method V) methods were developed. Methods (I-V) showed satisfactory results using TRL concentration ranges of 50–800 ng/mL, 2.5–80 μg/mL, 5–100 μg/mL, 5–100 μg/mL and 5–50 μg/mL, respectively. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 358.176 to 134.127 for TRL and m/z 340.18 to 116.08 for alogliptin (IS) were employed utilizing positive mode Electrospray Ionization (ESI). The degradation kinetic study (Method VI) was carried out using 1 N HCl based on three different temperatures (70 °C, 80 °C and 90 °C). Through the optimized method-3, a good chromatographic separation of TRL from its major degradation product was achieved. Arrhenius plot was used in the kinetic study and the apparent 1st order degradation rate constant (K), t1/2, t90, and the activation energies were calculated for each temperature and at 25 °C. The optimized UPLC-MS/MS method is suitable for further TRL assay either in biological fluids or in the presence of impurities.
Highlights
Trelagliptin (TRL) is a new antidiabetic drug that administered as a monotherapy for the treatment of diabetes mellitus and classified as one of dipeptidyl peptidase-4 (DPP-4) inhibitors
A validated HPLC-UV method was selected for a degradation kinetic study due to better separation for the degradation products and lower cost than LC-MS/MS method
The main rational behind the multifaceted analysis is to provide many varieties for the analyst to overcome the limitations of the different analytical systems as the high cost of LC-MS/MS for the developing countries, low sensitivity of UV spectrophotometry & the time consuming procedures dealing with the LC-UV methods from preparing different mobile phases to complex instrumentation
Summary
Trelagliptin (TRL) is a new antidiabetic drug that administered as a monotherapy for the treatment of diabetes mellitus (type II) and classified as one of dipeptidyl peptidase-4 (DPP-4) inhibitors. A validated HPLC-UV method was selected for a degradation kinetic study due to better separation for the degradation products and lower cost than LC-MS/MS method. No methods were found in literature dealing with TRL kinetic degradation study. The innovation of the underlying study is based on the multifaceted analysis for TRL in addition to a detailed kinetic degradation study. The alkaline degradation, 0.3% H2O2 oxidative degradation, UV light and heat stress conditions were checked for TRL with results in agreement with degradation outcomes from ALO7 with an identical chemical structure (Fig. 1a,b) except with a less fluorine atom. The obtained TRL degradation product (Fig. 1c) showed a similar degradation behavior to ALO in the acidic medium (Fig. 1d)
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