To describe the advantages and disadvantages of alternative matrices in the field of clinical and forensic toxicology.

A review of the characteristics and limitations of the most relevant alternative matrices have been conducted. Moreover, the main applications of the analysis of alternative matrices have been detail focusing on its usefulness in the resolution of real forensic and clinical cases.

The advance in more sensible testing methodologies have been permitted the analysis of other biological specimens, traditionally inaccessible. Different alternative biological matrices can be used in clinical and forensic toxicological cases to obtain additional information to those obtain by the analysis of traditional matrices. Moreover, these matrices can be used to resolve problems or impediments of traditional matrices, such as invasive sample collection, detection of long-term exposure, contamination or postmortem redistribution… Some of the most used alternative matrices nowadays are hair, oral fluid, meconium or vitreous humor. The main advantage of hair analysis is the possibility to extend the window of detection to months or even years and perform a chronological profile of drug consumption. Hair analysis is applied to cases of driving license regranting, drug-facilitated crimes, determination of gestational drug exposure or verification of drug-use history, among others. Its main limitation is the lack of dose/concentration correlation and the issue of external contamination. Oral fluid has a comparable window of detection with blood, but with an easier and non-invasive sample collection. However, oral fluid has a limited dose/concentration correlation and there is the possibility of buccal and passive exposure contamination. The use of oral fluid for investigating impaired driving at the roadside and for testing drug-use at workplace has exponentially increased recently, showing the potential of this matrix as an alternative to blood in detecting recent consumption. Meconium can provide information of in utero drug exposure from the second and mainly third trimester of pregnancy, with an easy and non-invasive collection. However, in some cases this matrix cannot be available, is a non-homogenous sample and require sensitive and complex methodologies. Finally, vitreous humor is a very interesting postmortem sample for determining ethanol, but also other drugs of abuse, due to it is anatomically isolated (minimizing postmortem redistribution) and protected from putrefaction. Vitreous humor volume is low and data about drug concentrations in this matrix is limited and the interpretation is complex.

The analysis of alternative matrices in isolation or in combination with traditional matrices can improve the resolution of clinical and forensic toxicological cases. The main advantages of alternative samples are an easy and non-invasive collection, while the main disadvantages are the necessity of sensitive methodologies and the lack of dose/concentration correlation. Moreover, the interpretation of the information provided by alternative matrices should be performed taking into account the characteristics of those samples.

The use of alternative matrices in clinical and forensic toxicology complements the information provide by traditional matrices, specially when traditional matrices are not available, their collection is invasive, or drugs are no longer detect in them.