title: Quantification of β-aminopropionitrile, an inhibitor of lysyl oxidase activity, in plasma and tumor of mice by liquid chromatography tandem mass spectrometry.
abstract: Lysyl oxidase enzymes are reported to be involved in patho-physiological process such as tumorigenesis. β-Aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase activity, suggesting a potentially useful therapeutic of interest in oncology. This paper describes the first assay concerning the quantification of BAPN by mass spectrometry. A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay was developed for the quantification of BAPN in plasma and tumor of mice. This method combines dansyl chloride (Dns) derivatization and extraction using a solid-phase extraction Oasis Max column. Deuterated BAPN was used as internal standard (IS). Separation was achieved using an C₁₈ column HypersylGold, (ThermoElectron), 3.0 µm (100 × 2.1 mm i.d.). Gradient elution with water containing 0.1% acetic acid (A) and acetonitrile containing 0.1% acetic acid (B) was applied. Detection was performed with an electrospray ionization interface operating in negative ion mode. Selected reaction monitoring was used with ion transitions m/z 302 → 249 for BAPN-Dns and m/z 306 → 250 for the IS. The method was fully validated in plasma and was linear and sensitive in the range of 10-500 ng/mL. The lower limit of quantification in plasma was 2.5 ng/mL. This validated assay was successfully applied to a kinetic study of BAPN in mouse plasma and demonstrates that BAPN reaches the tumoral tissue.
authors.affiliation: Hospices Civils de Lyon, F-69495, Pierre Bénite, France; Université de Lyon, F-69373, Lyon, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Machon
authors.forename: Benjamin
authors.initials: B
authors.lastname: Le Calve
authors.forename: Sylvie
authors.initials: S
authors.lastname: Coste
authors.forename: Mirella
authors.initials: M
authors.lastname: Riviere
authors.forename: Léa
authors.initials: L
authors.lastname: Payen
authors.forename: David
authors.initials: D
authors.lastname: Bernard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guitton
mesh_terms: D000629:Aminopropionitrile / Q000032:analysis / Q000097:blood* / Q000737:chemistry; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D051379:Mice; D009374:Neoplasms, Experimental / Q000737:chemistry*; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000629:Aminopropionitrile; D008249:Protein-Lysine 6-Oxidase
keywords: BAPN; lysyl oxidase (LOX); tandem mass spectrometry