title: Development and validation of LC-MS/MS with in-source collision-induced dissociation for the quantification of pegcantratinib in human skin tumors.
abstract: OBJECTIVE
  Pegcantratinib is a mini-PEGylated K252a derivative, under clinical evaluation as an anticancer agent acting through inhibition of the tropomyosin receptor kinase. A method for quantifying pegcantratinib in skin tumor biopsies of patients was required to determine tumor drug penetration.
  
  
  RESULTS
  A sensitive and PEGylated molecule specific HPLC-MS/MS method coupled with in-source collision-induced dissociation was developed. The method exhibited excellent precision (coefficient of variation ≤8.5%), accuracy in the range 95-102%, high and consistent recovery and no matrix effect. The assay was linear across a range of 1-500 ng/ml, with a limit of quantitation of 2.5 ng/ml.
  
  
  CONCLUSIONS
  We have developed and validated a method for analyzing pegcantratinib in human tumor biopsies, with the approach successfully applied to clinical trial samples.
authors.affiliation: Newcastle Cancer Centre Pharmacology Group, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Monique
authors.initials: M
authors.lastname: Zangarini
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Rajan
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Danilenko
authors.affiliation: Newcastle Cancer Centre Pharmacology Group, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Berry
authors.affiliation: Creabilis Therapeutics, Colleretto Giacosa, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Traversa
authors.affiliation: Newcastle Cancer Centre Pharmacology Group, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Veal
mesh_terms: D002227:Carbazoles / Q000032:analysis* / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000032:analysis* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D011092:Polyethylene Glycols; C049985:staurosporine aglycone
keywords: LC–MS/MS; PEGylation; pegcantratinib; tropomyosin receptor kinase A; tumor