Bioanalysis Zone

Pharmacokinetics of diphenylboroxazolidones of L-α-amino acids with activity on the CNS: quantification in rat DBS by UPLC–MS/MS


Background: A growing number of boron-containing compounds exhibit many important biological activities; of particular interest are the α-amino acid borinic derivatives with activity in the CNS. A validated, sensitive and specific UPLC–MS/MS technique for quantification of the diphenylboroxazolidones of glycine (DBPX-gly), L-aspartate (DPBX-L-asp) and L-glutamate (DPBX-L-glu) in dried blood spots (DBSs) is presented. Results: The most intense signal corresponds to compounds with 11B. The extraction procedure was liquid elution of 3.2-mm punched DBSs with acetonitrile:aqueous formic acid 0.1% (80:20 v/v). Assays proved to be linear, falling accurately and precisely within the range of 0.3–50 µg/ml for DPBX-L-asp and DPBX-L-glu and 0.1–5 µg/ml for DBPX-gly. Chromatograms exhibit clean 2.0-min running time peaks and S/N ratios for the LLOQ were approximately 15:1. The technique was used to evaluate the pharmacokinetics of the molecules and to correlate these with timecourse toxic effects. Conclusion: DBSs represent an advantage for the collection of small volumes of samples, and also in terms of processing and storage. UPLC–MS/MS allow us not only to identify the isotopic pattern of boron in DBPX, but also to quantify them with accuracy and specificity. Pharmacokinetics of these molecules exhibit a high apparent volume of distribution; it suggests a preference of DPBX-amino acids for fatty tissues such as the CNS.

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