Chromatographic separation of tiropramide hydrochloride and its degradation products along with their structural characterization using LC-QTOF-MS/MS and NMR

Abstract

Tiropramide HCl, an antispasmodic drug is subjected to various stress conditions (hydrolytic, oxidative, photolytic and thermal) as per ICH guidelines. The drug is widely used as an antispasmodic agent but there were no comprehensive degradation studies reported on it. Hence, forced degradation studies of tiropramide HCl were carried out to establish the degradation profile and the storage conditions to maintain its quality attributes during the shelf life and usage. A selective HPLC method was developed to separate the drug as well as all of its degradation products using Agilent C18 (250×4.6 mm; 5 µm) column. The mobile phase of 10mM ammonium formate at pH 3.6 (solvent A) and methanol (solvent B) with gradient elution at a flow rate of 1.00 mL/min was used. Tiropramide was susceptible to acidic, basic hydrolytic exposure and oxidative stress conditions in the solution. This drug was found to be stable in neutral, thermal and photolytic conditions in both solution and solid-state. Five degradation products were detected under different stress conditions. The mass spectrometric fragmentation pattern of tiropramide and its degradation products was extensively studied using LC-Q-TOF-MS/MS for their structural characterization. The position of the oxygen atom in the N-oxide degradation product was confirmed by NMR studies. The knowledge gained by these studies was used to predict drug degradation profiles which is helpful in the development of the dosage form.

Identification, characterisation and in silico ADMET prediction of ozenoxacin and its degradation products using high‐performance liquid chromatography‐photodiode array and liquid chromatography‐quadrupole time‐of‐flight‐tandem mass spectrometry

“…OXC was stable in acidic, basic and neutral hydrolysis conditions; during oxidation with 5% H 2 O 2 ; and in photolytic and thermal degradation. Liquid chromatography‐electrospray ionisation‐quadrupole time‐of‐flight‐tandem mass spectrometry (LC‐ESI‐QTOF‐MS/MS) was employed in positive ionisation mode to analyse OXC and its identified DPs 14 . The mechanism of DP formation was elucidated through a mechanistic explanation 15 .…”

“…Liquid chromatographyelectrospray ionisation-quadrupole time-of-flight-tandem mass spectrometry (LC-ESI-QTOF-MS/MS) was employed in positive ionisation mode to analyse OXC and its identified DPs. 14 The mechanism of DP formation was elucidated through a mechanistic explanation. 15 Method validation was performed in accordance with ICH recommendations Q2(R1).…”