Quantification of β‐aminopropionitrile, an inhibitor of lysyl oxidase activity, in plasma and tumor of mice by liquid chromatography tandem mass spectrometry. (14th January 2014)

• Record Type: Journal Article
• Authors: Machon, Christelle; Le Calve, Benjamin; Coste, Sylvie; Riviere, Mirella; Payen, Léa; Bernard, David; Guitton, Jérôme
• Is Part Of: Biomedical chromatography. Volume 28:Number 7(2014:Jul.)
• Page Start: 1017
• Page End: 1023
• Publication Date: 2014-01-14
• Subjects: Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.3110
• Languages: English
• ISSNs: 0269-3879

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Lysyl oxidase enzymes are reported to be involved in patho‐physiological process such as tumorigenesis. <italic>β</italic>‐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<sup>©</sup> Max column. Deuterated BAPN was used as internal standard (IS). Separation was achieved using an C<sub>18</sub> 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 <italic>m</italic>/<italic>z</italic> 302 → 249 for BAPN–Dns and <italic>m</italic>/<italic>z</italic> 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. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>