LC–MS/MS Quantification of Asymmetric Dimethyl Arginine and Symmetric Dimethyl Arginine in Plasma Using Surrogate Matrix and Derivatization with Fluorescamine

ABSTRACT

Aim: A novel LC–MS/MS method using a surrogate matrix and derivatization with fluorescamine was developed and validated for simultaneous quantification of asymmetric dimethyl arginine and symmetric dimethyl arginine. Methods & results: Asymmetric dimethyl arginine, symmetric dimethyl arginine and corresponding internal standards were extracted using protein precipitation and derivatization with fluorescamine followed by SPE. Derivatives were analyzed by turbo ion spray LC–MS/MS in the positive ion mode. Methodology was successfully transferred across multiple preclinical species and utilized in the support of several investigative studies. Conclusion: A new LC–MS/MS analytical methodology that utilizes a surrogate matrix and derivatization with fluorescamine was successfully developed and validated.

Keywords:

• ADMA
• derivatization
• fluorescamine
• parallelism
• SDMA

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2144/000112170

Acknowledgments

The authors would like to acknowledge Y Qian, M Szapacs and C Evans for reviewing this manuscript and providing valuable comments.

Financial & competing interests disclosure

The authors V Junnotula and S Gorman are employees of GSK and owners of GSK stocks. The authors B Jones, D Mulvana and M Shen are employees of Q Squared Solutions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This research work was funded by GlaxoSmithKline (GSK). Method development and investigative work was carried out at GSK and full validation was performed at Q squared solutions. Before submission, the manuscript underwent institutional review and approval process at both GSK and Q² solutions. Authors obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.