Stability of analytes in biosamples—an important issue in clinical and forensic toxicology?

Abstract

Knowledge of the stability of drugs in biological samples is important for the interpretation of toxicological findings. This paper reviews data on the stability of drugs in blood, plasma, or serum. Since such data have already been reviewed for classic drugs of abuse, the focus here is on newer drugs of abuse and on therapeutic drugs. Key information about the conditions of the stability experiments will be provided and the following drugs or drug classes are covered: amphetamines, amphetamine-derived, piperazine-derived, and phenethylamine-derived designer drugs, antidepressants, neuroleptics, anti-HIV drugs, antiepileptics, cardiovascular drugs, and others. In addition, aspects of stability experiments and their evaluations are discussed. The data presented show that the majority of drugs are stable in blood, plasma, or serum samples under the conditions usually encountered in a clinical or forensic toxicology laboratory. Instability usually only occurs for drugs carrying ester moieties, sulfur atoms, or other easily oxidized or reduced structures. Nevertheless, clinical or forensic specimens should always be stored at least in the refrigerator and preferably at -20 degrees C or lower to avoid any degradation. Finally, results obtained from biosamples that have been stored at room temperature for a longer time should be interpreted with great care and partial degradation should always be considered.

Zopiclone degradation in biological samples : Characteristics and consequences in forensic toxicology

“…Method validation includes several analytical parameters; selectivity, calibration model, accuracy (bias) and precision, limit of detection (LOD), lower limit of quantification (LLOQ), recovery/extraction efficiency and parameters affected by specimen composition such as matrix effects and stability [17][18][19][20][21][22]. Analytical result showing presence or absence of a drug in the specimen yields information relevant to the time of analysis and the stability of the drug in the actual matrix has to be considered in connection with result interpretation [23].…”

“…In forensic toxicology, the analyte can be a drug, metabolite and/or a degradation product in the biological matrix such as whole blood, serum, plasma, urine, hair, oral fluids or tissues. The knowledge of stability of a drug and its major metabolites in biological specimens is very important in forensic cases for the interpretation of analytical results [8,23,25]. Overestimation or underestimation of unreliable results may lead to erroneous conclusions in the judicial inquiry.…”

“…Instability can depend on physical (e.g. type of tubes and preservatives, light, temperature), chemical (hydrolysis, oxidation) or metabolic processes (enzyme activities and/or metabolic production) [2,8,23]. The duration of storage starts from the time of sampling and proceeding until the time of analysis.…”

¿Cuál es la utilidad clínica de un estudio toxicológico?

“…Si inicialmente se pidieron exámenes del primer nivel y posteriormente se requieren análisis de segundo nivel, éstos deben ser realizados en las mismas muestras tomadas al ingreso 6 . Por esta razón, el laboratorio debe tener procedimientos escritos para el correcto almacenamiento y preservación de las muestras, que por lo general pueden mantenerse refrigeradas 7 . En pacientes en que por la naturaleza del cuadro clínico se les realiza lavado gástrico, el contenido del primer lavado debe ser guardado refrigerado para incluirlo en un posterior estudio toxicológico avanzado.…”

“…Es imperativo recordar que un retraso en tomar las muestras requeridas va a disminuir el valor de un estudio toxicológico posterior y se puede perder información extremadamente valiosa 5,7 .…”