Quantification of β-aminopropionitrile, an inhibitor of lysyl oxidase activity, in plasma and tumor of mice by liquid chromatography tandem mass spectrometry

Christelle Machon, Benjamin Le Calve, Sylvie Coste, Mirella Riviere, Léa Payen, David Bernard, Jérôme Guitton

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1017-23
Number of pages7
JournalBiomedical chromatography : BMC
Volume28
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Aminopropionitrile
Protein-Lysine 6-Oxidase
Liquid chromatography
Tandem Mass Spectrometry
Liquid Chromatography
Mass spectrometry
Tumors
Plasmas
Neoplasms
Assays
Acetic Acid
Ions
Physiological Phenomena
Electrospray ionization
Oncology
Solid Phase Extraction
High performance liquid chromatography
Mass Spectrometry
Carcinogenesis
Negative ions

Keywords

  • Aminopropionitrile
  • Animals
  • Chromatography, Liquid
  • Drug Stability
  • Linear Models
  • Mice
  • Neoplasms, Experimental
  • Protein-Lysine 6-Oxidase
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry
  • Journal Article

Cite this

Machon, Christelle ; Le Calve, Benjamin ; Coste, Sylvie ; Riviere, Mirella ; Payen, Léa ; Bernard, David ; Guitton, Jérôme. / Quantification of β-aminopropionitrile, an inhibitor of lysyl oxidase activity, in plasma and tumor of mice by liquid chromatography tandem mass spectrometry. In: Biomedical chromatography : BMC. 2014 ; Vol. 28, No. 7. pp. 1017-23.
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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.",
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Quantification of β-aminopropionitrile, an inhibitor of lysyl oxidase activity, in plasma and tumor of mice by liquid chromatography tandem mass spectrometry. / Machon, Christelle; Le Calve, Benjamin; Coste, Sylvie; Riviere, Mirella; Payen, Léa; Bernard, David; Guitton, Jérôme.

In: Biomedical chromatography : BMC, Vol. 28, No. 7, 2014, p. 1017-23.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Quantification of β-aminopropionitrile, an inhibitor of lysyl oxidase activity, in plasma and tumor of mice by liquid chromatography tandem mass spectrometry

AU - Machon, Christelle

AU - Le Calve, Benjamin

AU - Coste, Sylvie

AU - Riviere, Mirella

AU - Payen, Léa

AU - Bernard, David

AU - Guitton, Jérôme

N1 - Copyright © 2014 John Wiley & Sons, Ltd.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Aminopropionitrile

KW - Animals

KW - Chromatography, Liquid

KW - Drug Stability

KW - Linear Models

KW - Mice

KW - Neoplasms, Experimental

KW - Protein-Lysine 6-Oxidase

KW - Reproducibility of Results

KW - Sensitivity and Specificity

KW - Tandem Mass Spectrometry

KW - Journal Article

U2 - 10.1002/bmc.3110

DO - 10.1002/bmc.3110

M3 - Article

C2 - 24424787

VL - 28

SP - 1017

EP - 1023

JO - Biomedical chromatography : BMC

JF - Biomedical chromatography : BMC

SN - 0269-3879

IS - 7

ER -