A Bioanalytical Liquid Chromatography Tandem Mass Spectrometry Approach for the Quantification of a Novel Antisense Oligonucleotide Designed for Parkinson's Disease: A Rat Brain Biodistribution Study.

IF 4.9 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2025-02-05 eCollection Date: 2025-02-14 DOI:10.1021/acsptsci.4c00698

Anastasia Palaiologou, Marianna Naki, Marina Pantazopoulou, Fedon-Giasin Kattan, Leonidas Stefanis, Epaminondas Doxakis, Constantin Tamvakopoulos

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引用次数: 0

Abstract

Antisense oligonucleotides (ASOs) represent a unique category of therapeutics targeting disease-related RNAs. Since this new therapeutic category emerged, the immediate need to analyze ASOs in clinically relevant biological matrices has led to several methodologies, such as ligand binding assays and imaging techniques. To overcome issues in specificity and provide exact quantitative data for ASOs, a new LC-MS/MS method was developed to analyze in brain tissue a novel 4-10-4 gapmer ASO with the potential for treating Parkinson's disease with phosphorothioated backbone and 2'-O-(2-methoxyethyl) modifications. The sample pretreatment protocol to extract the ASO from brain tissue employed solid phase extraction (SPE) and protein digestion. The LC-MS/MS method was fully optimized, validated and applied to quantify the target ASO in brain tissue samples following an in vivo brain distribution study. The method has a Lower Limit Of Quantification of 1 ng/mg and was applied to the study's samples, demonstrating satisfactory sensitivity and providing valuable information about the ASO's distribution in different brain regions over 45 days.

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.