title: Quantitative assay of capreomycin oleate levels in a drug formulation for inhalation with a fully validated HPLC method.
abstract: Capreomycin sulfate (CS), a mixture of 4 closely related compounds (powder mainly comprised of 2 forms), commonly injected intramuscularly is intended to be administer by inhalation for the treatment of pulmonary tuberculosis. In order to increase the drug residence time in the lung, capreomycin hydrophobicity was enhanced by substituting sulfate with oleate, thus obtaining capreomycin oleate (CO). The generation of a more hydrophobic ion-pair allows the reduction of the drug solubilisation in the bronchoalveolar fluids as well as its systemic absorption. The aim of the present study was to quantify CO in an in-house prepared drug formulation for inhalation. In this regard, a Hydrophilic Liquid Interaction Chromatography (HILIC) method was optimized with acetonitrile (ACN)/water containing eluents and a diol-type stationary phase. The optimal eluent composition [ACN/water-80/20 (v/v), 20mM ammonium formate, 3.0 wspH] produced a good separation (α equal to 1.15) between the two main peaks. The developed HILIC method succeeded in the quantitative assay of CO in the drug formulation and was fully validated. Very good precision and accuracy in the short- and long-period along with appreciably low LOD and LOQ values (respectively 1.75 and 5.25μg/mL) turned out.
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ianni
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Schoubben
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Montesano
authors.affiliation: Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Boulevard du Triomphe, CP-207, Campus de la Plaine, B-1050 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Lina
authors.initials: L
authors.lastname: Cossignani
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy. Electronic address: roccaldo.sardella@unipg.it.
authors.forename: Roccaldo
authors.initials: R
authors.lastname: Sardella
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, via Fabretti 48, 06123 Perugia, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Natalini
mesh_terms: D000280:Administration, Inhalation; D002207:Capreomycin / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D004339:Drug Compounding; D019301:Oleic Acid / Q000032:analysis* / Q000737:chemistry; D015203:Reproducibility of Results
chemical_list: D002207:Capreomycin; D019301:Oleic Acid
keywords: Capreomycin oleate; Dry powder for inhalation; Hydrophilic interaction liquid chromatography; Method validation