title: Validation protocol of analytical procedures for quantification of drugs in polymeric systems for parenteral administration: dexamethasone phosphate disodium microparticles.
abstract: In this work a protocol to validate analytical procedures for the quantification of drug substances formulated in polymeric systems that comprise both drug entrapped into the polymeric matrix (assay:content test) and drug released from the systems (assay:dissolution test) is developed. This protocol is applied to the validation two isocratic HPLC analytical procedures for the analysis of dexamethasone phosphate disodium microparticles for parenteral administration. Preparation of authentic samples and artificially "spiked" and "unspiked" samples is described. Specificity (ability to quantify dexamethasone phosphate disodium in presence of constituents of the dissolution medium and other microparticle constituents), linearity, accuracy and precision are evaluated, in the range from 10 to 50 μg mL(-1) in the assay:content test procedure and from 0.25 to 10 μg mL(-1) in the assay:dissolution test procedure. The robustness of the analytical method to extract drug from microparticles is also assessed. The validation protocol developed allows us to conclude that both analytical methods are suitable for their intended purpose, but the lack of proportionality of the assay:dissolution analytical method should be taken into account. The validation protocol designed in this work could be applied to the validation of any analytical procedure for the quantification of drugs formulated in controlled release polymeric microparticles.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martín-Sabroso
authors.forename: Daniel Filipe
authors.initials: DF
authors.lastname: Tavares-Fernandes
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Espada-García
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Torres-Suárez
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000737:chemistry; D007263:Infusions, Parenteral / Q000379:methods; D011108:Polymers / Q000737:chemistry*; D012680:Sensitivity and Specificity; D012995:Solubility
chemical_list: D011108:Polymers; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone
keywords: Analytical procedure; Dexamethasone phosphate disodium; Microparticles; Polymeric drug delivery systems; Validation protocol