Development and Validation of a Novel Stability-Indicating RP-HPLC Method for Simultaneous Determination of Tezacaftor and Ivacaftor in Fixed Dose Combination

Abstract

A simple and precise novel stability-indicating method for the simultaneous estimation of tezacaftor and ivacaftor in combined tablet dosage form was developed and validated using reversed-phase high-performance liquid chromatography (RP-HPLC). The method is being reported for the first time and includes an estimation of degradation products produced post-stress conditions without any extraction or derivatization. The chromatographic separation of the drugs was achieved with a Symmetry Shield RP18 Column (100 Å, 5 μm, 4.6 mm × 250 mm) using a mixture of buffer, methanol and acetonitrile (42:27:31 v/v/v) as mobile phase. The buffer used in mobile phase contained 35 mM potassium dihydrogen phosphate, and its pH was adjusted to 7.0 ± 0.02 with 20% orthophosphoric acid. The instrument was set at flow rate of 1.2 mL min−1 at ambient temperature and the wavelength of UV-visible detector at 275 nm. The developed method could be suitable for the quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. Stress testing was performed to prove the specificity. No interference was observed from its stress degradation products. The statistical analysis was done by using F-test and t-test at 95% confidence level.

Multiple Reaction Monitoring Mass Spectrometry for the Drug Monitoring of Ivacaftor, Tezacaftor, and Elexacaftor Treatment Response in Cystic Fibrosis: A High-Throughput Method

“…Although Singh et al have recently reported a HPLC method for the quantification of tezacaftor and ivacaftor, our method herein allows for a faster and low-dose high-throughput analysis with the inclusion of important active and partially metabolites as well as the inclusion of the novel triple combination. 27 Targeted method MRM-MS analysis such as the method described herein requires knowledge of the molecular weight of the analytes and their fragmentation behavior: ivacaftor 393 > 337 > 172 > 319 m/z, ivacaftor-M1 408.5 > 353 > 172 > 335.1 m/z, ivacaftor-M6 423 > 367 > 349 m/z, tezacaftor 521.1 > 440 > 130.9 > 222.9 m/z and elexacaftor 597.7 > 422 > 205 > 329 m/z under collision-induced dissociation (CID) conditions (Tables 3 and 4). By combining carefully selected MRM precursor and fragment ion pairs, MRM can be used to determine, highly specifically and reproducibly, the absolute concentrations of ivacaftor and its metabolites, tezacaftor, and elexacaftor in biological samples.…”

“…We have previously reported analytical methods for the quantification of ivacaftor–lumacaftor patient samples; however, with standard treatment regimens shifting, we must adapt and optimize the reported methods. Although Singh et al have recently reported a HPLC method for the quantification of tezacaftor and ivacaftor, our method herein allows for a faster and low-dose high-throughput analysis with the inclusion of important active and partially metabolites as well as the inclusion of the novel triple combination . Targeted method MRM-MS analysis such as the method described herein requires knowledge of the molecular weight of the analytes and their fragmentation behavior: ivacaftor 393 > 337 > 172 > 319 m / z , ivacaftor-M1 408.5 > 353 > 172 > 335.1 m / z , ivacaftor-M6 423 > 367 > 349 m / z , tezacaftor 521.1 > 440 > 130.9 > 222.9 m / z and elexacaftor 597.7 > 422 > 205 > 329 m / z under collision-induced dissociation (CID) conditions (Tables and ).…”

Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase

“…Precisely weighed an appropriate amount of IVA-SNEDDS into a 100 mL volumetric flask, methanol added to dissolve, shaken well, and filtered through 0.45 μm membrane (Jinteng, Tianjin, China). 47 The above samples were used to determine the content of IVA according to the external standard method under “HPLC analysis”. All the experiments were performed in triplicate.…”

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

“…Bioanalytical studies were carried out with LC-MS/MS, and bulk and pharmaceutical formulation studies were performed with a UV detector in HPLC. In some similar studies in the literature, forced degradation studies were also carried out [17,21,24]. However, these HPLC methods were developed for simultaneous analysis and the authors conducted their degradation studies with a mixture solution of both analytes [17,21,24].…”

“…In some similar studies in the literature, forced degradation studies were also carried out [17,21,24]. However, these HPLC methods were developed for simultaneous analysis and the authors conducted their degradation studies with a mixture solution of both analytes [17,21,24]. So, it is difficult to determine which active substance belongs to the DPs by HPLC, in this way.…”