RT Journal Article
T1 LC–MS-MS Method for the Determination of Antidepressants and Benzodiazepines in Meconium
A1 López Rabuñal, Ángela
A1 Lendoiro Belío, Elena
A1 Concheiro, M.
A1 López-Rivadulla Lamas, Manuel
A1 Cruz Landeira, Angelines
A1 Castro Ríos, Ana de
K1 Antidepressant
K1 Benzodiazepine
K1 Pregnancy
K1 Meconium
K1 In utero exposure
K1 LC-MS/MS
AB An LC-MS-MS method for the determination of 14 benzodiazepines (BZDs) (alprazolam, α-hydroxyalprazolam, clonazepam, bromazepam, diazepam, nordiazepam, lorazepam, lormetazepam, oxazepam, flunitrazepam, 7-aminoflunitrazepam, triazolam, midazolam and zolpidem) and 15 antidepressants (ADs) (amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, norclomipramine, fluoxetine, norfluoxetine, sertraline, norsertraline, paroxetine, venlafaxine, desmethylvenlafaxine, citalopram and desmethylcitalopram) in meconium was developed and validated. Meconium samples (0.25 ± 0.02 g) were homogenized in methanol and subjected to mixed-mode cation exchange solid-phase extraction. Chromatographic separation was performed in reversed phase, with a gradient of 0.1% formic acid in 2 mM ammonium formate and acetonitrile. Two different chromatographic gradient methods were employed, one for the separation of ADs and another for BZDs. Analytes were monitored by tandem mass spectrometry employing electrospray positive mode in MRM mode (2 transitions per compound). Method validation included: linearity [n = 5, limit of quantification (LOQ) to 400 ng/g], limits of detection (n = 6, 1-20 ng/g), LOQ (n = 9, 5-20 ng/g), selectivity (no endogenous or exogenous interferences), accuracy (n = 15, 90.6-111.5%), imprecision (n = 15, 0-14.6%), matrix effect (n = 10, -73 to 194.9%), extraction efficiency (n = 6, 35.9-91.2%), process efficiency (n = 6, 20.1-188.2%), stability 72 h in the autosampler (n = 3, -8.5 to 9%) and freeze/thaw stability (n = 3, -1.2 to -47%). The method was applied to four meconium specimens, which were analyzed with and without hydrolysis (enzymatic and alkaline). The authentic meconium samples tested positive for alprazolam, α-hydroxyalprazolam, clonazepam, diazepam, nordiazepam, fluoxetine, norfluoxetine, clomipramine and norclomipramine. Therefore, the present LC-MS-MS method allows a high throughput determination of the most common BZDs and ADs in meconium, which could be useful in clinical and forensic settings.
PB Oxford University Press
SN 0146-4760
YR 2020
FD 2020
LK https://hdl.handle.net/10347/38672
UL https://hdl.handle.net/10347/38672
LA eng
NO López-Rabuñal, A., Lendoiro, E., Concheiro, M., López-Rivadulla, M., Cruz, A., & de-Castro-Ríos, A. (2020). LC-MS-MS Method for the Determination of Antidepressants and Benzodiazepines in Meconium. Journal of analytical toxicology, 44(6), 580–588. https://doi.org/10.1093/jat/bkaa012
DS Minerva
RD 29 abr 2026