The sample preparation is the most critical step involved in the bioanalytical process. When dealing with green analytical chemistry, sample preparation can be even more challenging. To fit the green analytical chemistry principles, efforts should be made toward the elimination or reduction of the use of toxic reagents and solvents, minimization of energy consumption and increased operator safety. The simplest sample preparations are more appropriate for liquid biological matrices with little interfering compounds such as urine, plasma and oral fluid. The same does not usually occur with complex matrices that require more laborious procedures. The present review discusses green analytical approaches for the analyses of drugs of abuse in complex biological matrices, such as whole blood, breast milk, meconium and hair.

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