期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 158, 期 -, 页码 38-46出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2018.05.012
关键词
Aromatic aldehydes; alpha-Dicarbonyls; AGEs; Fluorogenic derivatization; Human serum; Diabetic patients
资金
- Takeda Science Foundation
alpha-Dicarbonyl compounds (alpha-DCs) are very clinically important as they are considered as advanced glycation end products (AGEs) precursors and biomarkers for many chronic diseases such as diabetes and vascular diseases, in addition to their major role in progression of complications of such diseases. Aromatic aldehydes and ammonium acetate were productively used as a one-pot co-reagents for fluorogenic denvatization of alpha-DCs yielding fluorescent imidazole derivatives. Among the tried aromatic aldehydes, 4-carbomethoxybenzaldehyde yielded the products with best fluorescent characters. This approach for fluorogenic denvatization of alpha-DCs overcome the selectivity problem of the most commonly used denvatization reagent for alpha-DCs, alpha-diamino compounds, that can react unselectively with alpha-DCs and aldehydes. Separation of the formed imidazole derivatives of five alpha-DCs including glucosone, 3-deoxyglucosone, glyoxal, methyl glyoxal and dimethyl glyoxal together with ethylmethylglyoxal as an internal standard was carried out on an octyl column usinga mobile phase consisted of methanol-water (15:85, v/v%) containing 0.2% formic acid with time programed flow, followed by fluorescence detection at excitation/emission wavelengths of 310/410 nm. The method showed excellent sensitivity for the targeted alpha-DCs with limits of detections ranging from 0.4 to 5.0 nM in human serum. Simple protein precipitation procedure was used for human serum treatment yielding very good recovery (91-105%) for the targeted alpha-DCs. The developed method was fully validated, then applied to the analysis of the five above mentioned clinically important alpha-DCs in serum samples of healthy, diabetic, rheumatic and cardiac disorders human volunteers. Due to the excellent analytical features of the developed method, including high selectivity and sensitivity, it was able to detect the pattern of the targeted alpha-DCs serum levels under the investigated different clinical conditions. (C) 2018 Elsevier B. V. All rights reserved.
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