5). Exposure of pregnant women to drugs has serious consequences on the health of the fetus, which manifest themselves before and after birth. COC crosses the placenta without undergoing metabolism with direct action on the fetal vasculature causing vasoconstriction and urogenital, cardiovascular and central nervous system malformations (6). Tobacco use by the mother decreases the fetal growth rate, because it increases the level of carboxyhemoglobin in fetal blood. Moreover, the exposure to tobacco may induce abortion, placental abruption and sudden infant death syndrome during and after pregnancy (7). In utero drug exposure can be evaluated soon after birth by investigating analytes and metabolites in meconium samples. The assessment of this exposure is crucial to identify, treat and monitor newborns displaying symptoms typical of drug withdrawal. A qualitative or quantitative analysis of drugs, metabolites and biomarkers can be conducted in several types of biological matrices (conventional matrices), such as plasma, serum, whole blood, saliva, urine and tissues (8). Recently, studies have used alternative biological samples, such nails, hair, umbilical cord, amniotic fluid and meconium (9–11). Meconium, the first fecal matter passed by a neonate, begins to form at 12 weeks of gestation, which makes the specimen the biological matrix of choice for detecting in utero drug exposure. It is a heterogeneous and complex sample consisting of water, desquamated epithelial cells of the gastrointestinal tract and skin and various substances such as acids and bile salts, cholesterol, enzymes, sugars, proteins, pancreatic and intestina .....