title: New perspectives in bio-analytical techniques for preclinical characterization of a drug candidate: UPLC-MS/MS in in vitro metabolism and pharmacokinetic studies.
abstract: Lead optimization requires rapid bio-analytical turnover for the generation of early absorption, distribution, metabolism, excretion (ADME) and pharmacokinetics (PK) data maintaining a high quality level. Therefore, one of the major challenges in the bio-analytical field is to achieve faster and more sensitive quantification protocols. In the present communication, a comparison between HPLC and ultra performance liquid chromatography (UPLC) performances in terms of sensitivity and resolution is shown using a pharmakokinetic study and a metabolism study as models. The studies highlight the features of the new technology and the resulting impact in the PK throughput and in the characterization of isomeric metabolites using UPLC/MS/MS technique.
authors.affiliation: NiKem Research S.r.l., V. Zambeletti 25, 20021 Baranzate, Milano, Italy. samuele.pedraglio@nikemresearch.com
authors.forename: Samuele
authors.initials: S
authors.lastname: Pedraglio
authors.forename: Marco Giulio
authors.initials: MG
authors.lastname: Rozio
authors.forename: Paola
authors.initials: P
authors.lastname: Misiano
authors.forename: Veronica
authors.initials: V
authors.lastname: Reali
authors.forename: Giulio
authors.initials: G
authors.lastname: Dondio
authors.forename: Chiara
authors.initials: C
authors.lastname: Bigogno
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology; D002138:Calibration; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015925:Cryopreservation; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry; D014700:Verapamil / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: C514015:4-(5,6-dichloro-1H-indol-2-yl)-3-ethoxy-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide; D001549:Benzamides; D007211:Indoles; D014700:Verapamil