Pharmaceutica Analytica Acta

Abstract

Determination of Ketamine, Nor-Ketamine, Hydroxynor-ketamine, and Dehydronor-Ketamine by LC-MS/MS in Plasma with the Application of Green Analytical Chemistry Principles

Carla Maria de Sousa Silva, Luiz Carlos da Cunha, Mauricio Yonamine, Jose Luiz da Costa, Jeronimo Raimundo de Oliveira Neto, Naiara Raica Lopes de Oliveira

Introduction: Ketamine (KT) is a medication used in veterinary, pediatric, and ophthalmological medicine primarily as an anesthetic. In recent years, it has also been used recreationally and occasionally as a crime-facilitating drug. Additionally, KT exhibits effects similar to classical antidepressant drugs, making it a consideration in depression treatment. In the area of forensic toxicology, sample preparation is a relevant part of the analytical procedure; however, it is essential to consider aspects such as environmental responsibility, the use of clean methods, and sustainable development.

Objective: To optimize and validate a Liquid-Liquid Extraction (LLE) technique and a bioanalytical method based on the principles of Green Analytical Chemistry (GAC) to determine ketamine and some of its biotransformation products (norcetamine, hydroxynorcetamine, and dehydronorcetamine) in human plasma samples using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS).

Materials and methods: The study involved optimizing a bioanalytical method based on GAC principles for the determination of the analytes of interest, utilizing Ethyl Acetate (EtOAc) as the extracting solvent in LLE.

Results and discussion: The study's results indicate the effectiveness of the developed extraction technique and bioanalytical method, validated by LC-MS/MS, in quantifying plasma levels of KT, NK, HNK, and DHNK. The applicability to human plasma samples was confirmed by the effectiveness and satisfactory confidence limits in determining the analytes of interest. The findings align with conventional literature data, underscoring the method's viability for toxicological analyses. Furthermore, the study emphasizes the importance of environmental responsibility and sustainable development, emphasizing the need for more responsible practices to reduce negative environmental impacts from human activities and preserve natural resources for future generations.

Conclusion: Regarding the application of GAC principles, the extraction technique and bioanalytical method achieved 5 out of its 12 basic principles and can therefore be considered a valid alternative for toxicological analyses.

Published Date: 2024-03-04; Received Date: 2024-02-02