Simultaneous determination of 137 drugs of abuse, new psychoactive substances, and novel synthetic opioids in meconium by UHPLC-QTOF

Abstract

New psychoactive substances (NPS) have been introduced into the market in recent years, with new analytes reported every year. The use of these substances in women can occur at any stage of life, even in the childbearing age. Drug use during pregnancy presents significant risks for the mother and the fetus, so it is important to have tools that allow to detect prenatal exposure to these substances of abuse. Therefore, an analytical method for the determination of 137 NPS and other drugs of abuse in meconium by UHPLC-QTOF was developed and validated for semi-quantitative purpose. Linearity range, limit of detection (LOD), precision, matrix effect, selectivity, and specificity were evaluated. For all analytes, the calibration curves were studied in the ranges between 2, 10, or 50 ng/g and 750 or 1000 ng/g, (depending on the analyte) and the LOD ranged between 0.04 and 2.4 ng/g. The method was applied to 30 meconium specimens from cases in which fentanyl had been administered as epidural anesthesia at the time of delivery or cases in which the maternal hair was positive to other drug of abuse. Four meconium samples tested positive for fentanyl (range concentration = 440–750 ng/g) and two samples tested positive to acetylfentanyl (range concentration = 190–1400 ng/g).

Determination of Prenatal Substance Exposure Using Meconium and Orbitrap Mass Spectrometry

“…Interestingly, solely norfentanyl (n = 16) was identified and fentanyl was not detected even following a manual identification. Conversely, López-Rabuñal et al identified fentanyl in four meconium samples without norfentanyl (included in the screening) [21]. Ristimaa et al detected fentanyl in 2 out of 209 meconium samples, however they do not indicate if norfentanyl was screened for [17].…”

“…This method relies on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) and an in-house database containing 869 molecular drugs. More recently (2021), López-Rabuñal et al proposed another large screening devoted to new psychoactive substances (NPS) [21]. This method allows the simultaneous determination of 137 NPS in meconium by LC-HRMS.…”

New Psychoactive Substances: Which Biological Matrix Is the Best for Clinical Toxicology Screening?

“…Consumption of drugs of abuse during pregnancy increases the risk of premature delivery, fetal growth restriction, and neonatal abstinence syndrome. 33 Meconium has been used for decades to document prenatal exposure to abused drugs, but limited data are available about prenatal exposure to NPSs. 33 Recently, López-Rabuñal et al developed an analytical procedure for the determination of 137 NPSs and other drugs of abuse in meconium, consisting of homogenization, solid-phase extraction, and LC-HRMS/ MS analysis and reported acetylfentanyl detection in 2 of 30 meconium specimens.…”

Hair testing applied to the assessment of in utero exposure to drugs: Critical analysis of 51 cases of the University Hospital of Verona

“…[9][10][11] In particular, meconium is gaining increasing importance, as witnessed by the significant number of papers published in the last 10 years. 10,12 As it is well known, meconium is the first stool of a newborn and can provide specific information on the drug's foetal exposure. It shows a relatively wide detection window, covering the second and third trimesters of pregnancy.…”