ABSTRACT
Abstract Objectives: Cystic fibrosis (CF) is a severe autosomal recessive disease that results from mutations in a gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, a chloride channel. This study aims to characterize the clinical and genetic features of a cohort of pediatric people with CF (PwCF) in the center of Portugal and to determine which ones are candidates for the new drugs modulating the CFTR channel. Methods: A review of the demographic, genetic and clinical characteristics of PwCF undergoing follow-up at a CF reference center was carried out. Results: Twenty-three PwCF (12 male), with a median age of 12 years, were followed up. All patients carry the F508del mutation in at least one allele. Fifteen PwCF were F508del-homozygous, median BMI z-score was -0.13, all are pancreatic insufficient and median FEV1 value was 78.1%. These PwCF are eligible for dual therapy (lumacaftor/tezacaftor+ivacaftor) and for triple therapy (tezacaftor+ivacaftor+elexacaftor). PwCF with 711 +1G->T (n = 2), 2184insA (n = 1) mutations and a novel mutation c.3321dup (n = 1) have minimal function mutation and patients with a residual function mutation: R334W (n = 3) and P5L (n = 1) have a less severe phenotype. All these patients, because they also carry F508del mutation, are elegible to triple therapy. Conclusions: Genetic and molecular characterization of PwCF poses an important step not just for CF diagnosis and prognosis which is tightly correlated with the clinical phenotype, but also for the eligibility of CFTR modulator drugs.
ABSTRACT
Objective: Aim of the present research work was to develop a sensitive, rapid and accurate, stability-indicating RP-UPLC method for the simultaneous estimation of tezacaftor and ivacaftor in formulations. Methods: The chromatographic separation of the mixture of tezacaftor and ivacaftor was attained in isocratic method utilizing a mobile phase of 0.1 % orthophosphoric acid and acetonitrile in the proportion of 50:50%v/v utilizing a HSS C18 column which has dimensions of 100×2.1 mm, 1.7 m particle size and the flow rate of 0.3 ml/min. The detection system was monitored at 292 nm wavelength maximum with 1.5 ml injection volume. The present method was validated as per the guidelines given by the ICH for specificity, accuracy, sensitivity, linearity and precision. Results: The retaining time for tezacaftor and ivacaftor were achieved at 1.071 min and 0.530 min, respectively. Tezacaftor, ivacaftor and their combined drug formulation were exposed to thermal, acidic, oxidative, photolytic, and alkaline conditions. The developed method was highly sensitive, rapid, precise and accurate than the earlier reported methods. The total run time was decreased to 2.0 min; hence, the technique was more precise and economical. Stability studies directed for the suitability of the technique for degradation studies of tezacaftor and ivacaftor. Conclusion: The projected method can be utilized for routine analysis in the quality control department in pharmaceutical trades.