Fucosyl monosialoganglioside: Quantitative analysis of specific potential biomarkers of lung cancer in biological matrices using immunocapture extraction/tandem mass spectrometry. (31st July 2018)

• Record Type: Journal Article
• Authors: Ranasinghe, Asoka; Mehl, John; D'Arienzo, Celia; Nabbie, Fizal; Chiu, Christopher; Thevanayagam, Lourdes; Srinivasan, Mohan; Hogan, Jason; Ponath, Paul; Olah, Timothy
• Is Part Of: Rapid communications in mass spectrometry. Volume 32:Number 17(2018)
• Page Start: 1481
• Page End: 1490
• Publication Date: 2018-07-31
• Subjects: Mass spectrometry -- Periodicals; 543.65
• DOI: 10.1002/rcm.8194
• Languages: English
• ISSNs: 0951-4198

Abstract

Abstract : Rationale: Certain lung cancer patients express elevated Fucosyl Monosialoganglioside (Fuc‐GM1) in circulation compared to control groups. Several sensitive methods involving characterization of Fuc‐GM1 have been reported. However, a highly specific and sensitive method for quantifying multiple potential Fuc‐GM1 biomarkers present in various biological matrices has not been reported to date. Methods: Individual Fuc‐GM1 analogs in a commercially obtained standard mixture were characterized using HPLC/UV/MS and high‐resolution mass spectrometry (HRMS). Proprietary antibodies, mAb1 and mAb2, were used to selectively capture and pre‐concentrate the soluble and drug‐bound forms of Fuc‐GM1 molecules present in human serum and whole blood, eliminating the background matrix components. Immunocapture extraction (ICE) followed by HPLC/MS/MS was used to quantify specific Fuc‐GM1 analogs in biological matrices. Results: The concentration of individual Fuc‐GM1 analogs in the standard mixture was estimated to be 7–34%, using HPLC/UV/MS. Using the standard mixture spiked into the biological matrices (100 μL), the lower limit of quantification (LLOQ) of each analog was 0.2–0.4 ng/mL with a dynamic range of up to 200 ng/mL. The applicability of the ICE‐HPLC/MS/MS method was demonstrated by detecting endogenous Fuc‐GM1 analogs present in rat blood and in several lung cancer cell lines. Conclusions: This highly specific and sensitive HPLC/MS/MS method for quantifying individual potential Fuc‐GM1 biomarkers in serum and whole blood can play a critical role in patient stratification strategies and during drug treatment. This method can be employed for monitoring both free (soluble) form and antibody drug‐bound Fuc‐GM1.