A rapid LC-MS/MS method for the simultaneous quantification of ivacaftor, lumacaftor, elexacaftor, tezacaftor, hexyl-methyl ivacaftor and ivacaftor carboxylate in human plasma.

Autor: Zheng Y; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Rouillon S; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Khemakhem M; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Balakirouchenane D; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Lui G; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France; CIC 1419 Inserm, Cochin-Necker, Paris, France., Abdalla S; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Sanoufi MR; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Sauvaitre L; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Thebault L; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Hirt D; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Treluyer JM; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France; CIC 1419 Inserm, Cochin-Necker, Paris, France., Gana I; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Benaboud S; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France., Froelicher-Bournaud L; Pharmacologie et évaluation des thérapeutiques chez l'enfant et la femme enceinte URP 7323, Université Paris cité, Paris, France; Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France. Electronic address: leo.froelicherbournaud@aphp.fr.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Sep 15; Vol. 248, pp. 116322. Date of Electronic Publication: 2024 Jun 24.
DOI: 10.1016/j.jpba.2024.116322
Abstrakt: Cystic fibrosis is one of the most common genetic diseases among caucasian population. This disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding for the CFTR protein. Lumacaftor, elexacaftor, tezacaftor, and ivacaftor were currently used as the treatment to Cystic fibrosis. In this study, we describe a new method for the simultaneous quantification of four molecules: lumacaftor, elexacaftor, tezacaftor, and ivacaftor, alongside two metabolites of ivacaftor, specifically hexyl-methyl ivacaftor and ivacaftor carboxylate by liquid chromatography-tandem mass spectrometry. This method holds significant utility for therapeutic drug monitoring and the optimization of treatments related to CFTR modulators. Molecules were extracted from 100 µL of plasma by a simple method of protein precipitation using acetonitrile. Following extraction, chromatographic separation was carried out by reverse chromatography on a C18 analytical column, using a gradient elution of water (0.05 % formic acid, V/V) and acetonitrile (0.05 % formic acid, V/V). The run time was 7 minutes at a flow rate of 0.5 mL/min. After separation, molecules were detected by electrospray ionization on a Xevo TQD triple-quadrupole-mass-spectrometer (Waters®, Milford, USA). The calibration range were: 0.053-20.000 mg/L for elexacaftor, tezacaftor and lumacaftor, 0.075-14.000 mg/L for ivacaftor, and 0.024-6.500 mg/L for hexyl-methyl ivacaftor and ivacaftor carboxylate. The proposed method underwent throughout validation demonstrating satisfactory precision (inter- and intra-day coefficients of variation less than 14.3 %) and a good accuracy (inter- and intra-day bias ranging between -13.7 % and 14.7 %) for all the analytes. The presented method for the simultaneous quantification of CFTR modulators and their metabolites in human plasma has undergone rigorous validation process yielding good results including strong precision and accuracy for all analytes. This method has been effectively used in routine analytical analysis and clinical investigations within our laboratory.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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