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Detection of S-nitroso compounds by use of midinfrared cavity ring-down spectroscopy.

ABSTRACT: S-Nitroso compounds have received much attention in biological research. In addition to their role as nitric oxide donors, there is growing evidence that these compounds are involved in signaling processes in biological systems. Determination of S-nitrosylated proteins is of great importance for fundamental biological research and medical applications. The most common method to assay biological S-nitroso compounds is to chemically or photochemically reduce SNO functional groups to release nitric oxide, which is then entrained in an inert gas stream and detected, usually through chemiluminescence. We report a method of S-nitroso compound detection using cavity ring-down measurements of gaseous NO absorbance at 5.2 ?m. The proposed method, in contrast to the chemiluminescence-based approach, can be used to distinguish isotopic forms of NO. We demonstrated sensitivity down to ?2 pmol of S(14)NO groups and ?5 pmol of S(15)NO groups for S-nitroso compounds in aqueous solutions. The wide dynamic range of cavity ring-down detection allows the measurement of S-nitroso compound levels from pico- to nanomole amounts.

SUBMITTER: Stsiapura VI

PROVIDER: S-EPMC4519009 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Detection of S-nitroso compounds by use of midinfrared cavity ring-down spectroscopy.

Stsiapura Vitali I VI Shuali Vincent K VK Gaston Benjamin M BM Lehmann Kevin K KK

Analytical chemistry 20150303 6

S-Nitroso compounds have received much attention in biological research. In addition to their role as nitric oxide donors, there is growing evidence that these compounds are involved in signaling processes in biological systems. Determination of S-nitrosylated proteins is of great importance for fundamental biological research and medical applications. The most common method to assay biological S-nitroso compounds is to chemically or photochemically reduce SNO functional groups to release nitric ...[more]

PMID: 25692741

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Project description:New therapeutic biological entities such as bispecific antibodies targeting tissue or specific cell populations form an increasingly important part of the drug development portfolio. However, these biopharmaceutical agents bear the risk of extensive target-mediated drug disposition or atypical pharmacokinetic properties as compared to canonical antibodies. Pharmacokinetics and bio-distribution studies become therefore more and more important during lead optimization. Biologics present, however, greater analytical challenges than small molecule drugs due to the mass and selectivity limitation of mass spectrometry and ligand-binding assay, respectively. Radiocarbon (14C) and its detection methods, such as the emerging 14C cavity ring down spectroscopy (CRDS), thus can play an important role in the large molecule quantitation where a 14C-tag is covalently bound through a stable linker. CRDS has the advantage of a simplified sample preparation and introduction system as compared to accelerator mass spectrometry (AMS) and can be accommodated within an ordinary research laboratory. In this study, we report on the labeling of an anti-IL17 IgG1 model antibody with 14C propionate tag and its detection by CRDS using it as nanotracer (2.1 nCi or 77.7 Bq blended with the therapeutic dose) in a pharmacokinetics study in a preclinical species. We compare these data to data generated by AMS in parallel processed samples. The derived concentration time profiles for anti-IL17 by CRDS were in concordance with the ones derived by AMS and ?-counting of an 125I-labeled anti-IL17 radiotracer and were well described by a 2-compartment population pharmacokinetic model. In addition, antibody tissue distribution coefficients for anti-IL17 were determined by CRDS, which proved to be a direct and sensitive measurement of the extravascular tissue concentration of the antibody when tissue perfusion was applied. Thus, this proof-of-concept study demonstrates that trace 14C-radiolabels and CRDS are an ultrasensitive approach in (pre)clinical pharmacokinetics and bio-distribution studies of new therapeutic entities.

Dataset Information

Detection of S-nitroso compounds by use of midinfrared cavity ring-down spectroscopy.

Publications

Detection of S-nitroso compounds by use of midinfrared cavity ring-down spectroscopy.

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