Determination of ivacaftor by liquid chromatography techniques in pharmaceutical formulation with interlaboratory comparison and characterization of five novel degradation products by high‐performance liquid chromatography ion trap time‐of‐flight mass spectrometry

Abstract

Cystic fibrosis is a life‐threatening genetic disease that causes damage to the lungs. Ivacaftor, the first drug to target the underlying defect of the disease caused by specific mutations, improves outcomes and reduces hospitalizations. In this study, quantitative determination of ivacaftor was performed by liquid chromatography, while high‐resolution mass spectrometric analyses were performed for qualitative determination. The validation studies of the developed methods were performed according to International Conference on Harmonisation Q2(R1) guideline. Ivacaftor was separated from its degradation product by using Phenomenex Kinetex C18 (150 × 3 mm, 2.6 µm) column. The isocratic mobile phase for binary pump configuration was 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile (27:63) (v/v), pH = 2.5; the flow rate of 0.25 mL/min was used in all methods. In the degradation studies, five degradation products were identified using high‐performance liquid chromatography ion trap time‐of‐flight mass spectrometric analyses: three of them have never been reported up to date; whereas the other two were existing in the literature and they were having Chemical Abstracts Services registry numbers since they were synthesized before for various other purposes. Also, analysis of an in‐lab prepared chemical equivalent of Kalydeco® and interlaboratory comparison were performed.

HPLC method for simultaneous quantification of lumacaftor and ivacaftor bulk and pharmaceutical formulations

“…In fact, in previous methods developed for IVA or LUMA analysis (one of the authors also contributed), stability studies have shown that the active ingredients are quite stable [20,21]. However, in this study, stability studies were carried out meticulously because IVA and LUMA were mixed in the working solutions and ava contributed as IS.…”

Liquid chromatographic determination of lumacaftor in the presence of ivacaftor and identification of five novel degradation products using high‐performance liquid chromatography ion trap time‐of‐flight mass spectrometry

“…Another important point is that SIM is specific or selective. It is the determination of active pharmaceutical ingredient (API) in the presence of excipients, additives, and degradation products that are expected to be present in the specific SIM [9,10]. Selective SIM is the technique that measures API and all degradation products in the presence of excipients and additives [9,11,12].…”