ABSTRACT
A simple, rapid and accurate ultra-high performance liquid chromatographic (UHPLC) method with a UV detection for the determination of the chemical purity and assay of bimatoprost (BT-1) was developed. The chromatographic separation was achieved with the use of an Acquity BEH C8, 150â¯×â¯2.1â¯mm, 1.7⯵m reversed phase analytical column. The mobile phase consisted of 0.01% H3PO4: acetonitrile (initial conditions 80 : 20, v/v) was passed through the column at the flow rate of 0.7â¯mL min-1. The separation was carried out in the gradient elution mode. The presented method allows to separate ten potential impurities of BT-1. The full validation according to the ICH Q2 (R1) guidelines was carried out for five of the potential impurities while limit tests were performed for four BT-1 related substances. The performed validation tests proved the suitability of the method for its intended purposes. An additional LC/MS method was utilized for the identification of the unknown impurities in bimatoprost as well as the degradation impurities generated during the forced degradation studies.
Subject(s)
Bimatoprost/analysis , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Drug Contamination , Drug Stability , Acetonitriles/chemistry , Limit of Detection , Linear Models , Mass Spectrometry , Quality Control , Reproducibility of ResultsABSTRACT
Important information gaps remain on the efficacy and safety of drugs in children. Pediatric drug development encounters several ethical, practical, and scientific challenges. One barrier to the evaluation of medicines for children is a lack of innovative methodologies that have been adapted to the needs of children. This article presents our successful experience of pediatric microdose and microtracer studies using (14) C-labeled probes in Europe to illustrate the strengths and limitations of these approaches.
Subject(s)
Carbon Radioisotopes/administration & dosage , Clinical Trials, Phase I as Topic , Drug Approval , Pharmaceutical Preparations/administration & dosage , Age Factors , Carbon Radioisotopes/adverse effects , Carbon Radioisotopes/economics , Carbon Radioisotopes/pharmacokinetics , Child , Child, Preschool , Clinical Trials, Phase I as Topic/economics , Clinical Trials, Phase I as Topic/ethics , Clinical Trials, Phase I as Topic/legislation & jurisprudence , Dose-Response Relationship, Drug , Drug Approval/economics , Drug Approval/legislation & jurisprudence , Drug Costs , Drug Dosage Calculations , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Europe , Government Regulation , Humans , Infant , Infant, Newborn , Patient Safety , Pharmaceutical Preparations/economics , Pharmaceutical Preparations/metabolism , Pharmacokinetics , Risk Assessment , Risk FactorsABSTRACT
The potential of capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection for the separation and determination of dimethylamine (DMA) and other low-molecular-mass amines involving precolumn derivatization with fluorescein isothiocyanate isomer I (FITC) was investigated. Different variables that affect derivatization (pH, FITC concentration, reaction time and temperature) and separation (buffer concentration, addition of various organic modifiers, applied voltage and length of capillary) were studied. The linearity, reproducibility and reliability of the method were evaluated. The estimated instrumental detection limit for a 2-s pressure injection of the FITC-DMA derivative was 50 pg/ml (10(-9) M), using LIF detection with excitation and emission wavelengths of 488 nm and 520 nm, respectively. However, for practical reasons, a minimum of 5 ng/ml DMA should be subjected to the derivatization. The applicability of the described method to the extract of atmospheric aerosol samples was demonstrated.
