In vitro studies on the dependence of drug deposition in dentin on drug concentration, contact time, and the physicochemical properties of the drugs

Abstract

The chemical analysis of dental hard tissues can provide information on previous drug use due to the deposition of drugs into this tissue. For the interpretation of analytical results in, e.g., postmortem toxicology or regarding archeological samples, the influence of drug dosing, consumption frequency, duration of intake and type of drug on analyte concentrations in teeth has to be characterized. To approximate these correlations, in vitro models were applied to investigate the time dependency of drug deposition via and against pulp pressure (perfusion studies) and the concentration dependency of drug deposition via oral cavity (incubation study) as well as the influence of de- and remineralization (pH cycling) on the incorporation of drugs in bovine dentin pellets. Some of the drugs of abuse most relevant in forensic case work (amphetamines, opiates, cocaine and benzoylecgonine) were applied. Concentrations in dentin samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after pulverization and extraction via ultrasonication with methanol. The studies showed that drug deposition in dentin likely depends on the physicochemical properties of the drug molecules as well as on the duration of contact with drugs via the blood stream and on drug concentrations present in the oral cavity. Higher drug concentrations in teeth can result from a more frequent or longer drug use. In addition, intake of higher doses or oral/inhalative consumption can also be expected to lead to higher drug concentrations. These findings can be helpful for the interpretation of postmortem cases.

Keywords: Alternative matrices; Dental hard tissues; Forensic toxicology; Illicit drugs; LC–MS/MS; Teeth.

Fig. 1

Experimental setup of the counterperfusion with drug-containing remineralization solution

Fig. 2

Mean concentrations of model drugs in demineralized dentin pellets (n = 3) after different times of incubation in drug-containing remineralization solution (1, 3 and 6 µg/mL). Due to analytical problems 6-MAM could not be analyzed after 1 week using the drug solution with a concentration of 1 µg/mL

Fig. 3

Mean concentrations of model drugs in demineralized dentin pellets (n = 3) after 9 days pH cycling with different concentrations of drug-containing remineralization solution