GENOTYPING OF VOLUNTEERS FOR NAPROXEN PHARMACOKINETIC ASSAYS AND MOBILE PHASE STANDARDIZATION IN UHPLC

抄録

Background: Individual responses to nonsteroidal anti-inflammatory drugs (NSAIDs) are influenced by a combination of pharmacokinetic and pharmacodynamic factors (PK / PD) that may undergo a regulatory influence on some genetic factors, and this is the way to customize prescriptions today, with satisfactory effectiveness and minimal side effects. Genetic polymorphisms for the efficacy of inflammatory signal control and NSAID toxicity have not yet been fully elucidated. The main objective of this study was to genotype the volunteers for CYP2C9 to correlate with future pharmacokinetic data of naproxen in saliva samples analyzed by UHPLC.

Methods: For this proposal, 23 volunteers were genotyped for CYP2C9 using DNA from saliva samples. These volunteers will make subsequent collections for a pharmacokinetic study after taking a naproxen tablet in a later stage of this research. The mobile phase standardization was performed for the subsequent assays. For pharmacokinetic assays, the saliva samples will undergo UHPLC analysis.

Results: Salivary DNA analyses showed 19 non-mutated volunteers for CYP2C9 (CYP2C9 *1 / *1) and 4 mutated heterozygous volunteers (1 volunteer CYP2C9 *1 / *2 and 3 volunteers CYP2C9 *1 / *3), no mutated homozygotes were found (CYP2C9 *2 / *2 or CYP2C9 * 3 / *3). The mobile phase chosen for the subsequent analyzes was 0.1 M phosphate buffer and acetonitrile (70:30) and the pH was adjusted with 0.1 M orthophosphoric acid (pH 3.2) while the C18 column was maintained at 24oC. Lastly, a flow rate of 1.0 mL/min, with an injection volume of 70 uL was used.

Conclusions: Fifteen non-mutaded volunteers will be part of the sample for pharmacokinetic assays, but recruitment of new volunteers will be required to increase the number of mutated volunteers for CYP2C9. The selected mobile phase will allow rapid and accurate analysis of the concentrations of naproxen in the saliva samples.