# Evaluation of Therapeutic Opioids in Hair of Neonatal and Pediatric Patients

## TL;DR

This study examines how opioids and their metabolites are incorporated into the hair of neonatal and pediatric patients, providing data to improve forensic interpretations.

## Contribution

The study establishes opioid concentration ranges and metabolite ratios in pediatric hair, which is novel for this population.

## Key findings

- Opioids like fentanyl, sufentanil, and morphine were detected in pediatric hair with measurable concentrations.
- Metabolite ratios, such as β-hydroxyfentanyl to fentanyl, were found to be useful for distinguishing drug intake from contamination.
- Significant correlations were observed between administered opioid doses and concentrations in hair.

## Abstract

Forensic hair analysis poses a valuable tool for assessing opioid exposure in children and neonates. However, reliable literature data on opioid concentrations in the hair of this population are mostly scarce, making the interpretation of such hair analysis results rather challenging. This noninterventional study aims to address this issue by investigating 118 hair samples of pediatric patients (median age: 50 days) from the University Children's Hospital Zurich. These patients were treated with medically approved novel synthetic opioids (fentanyl, remifentanil, sufentanil, or alfentanil) and traditional opioids (morphine, methadone, and hydromorphone) during their clinical treatment. Quantification of the opioids and selected metabolites was achieved by a previously validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) based method, which showed good sensitivity with lower limits of quantification (LLOQs) ranging from 0.1 to 1 pg/mg hair. Most analytes were successfully detected in patients' hair, with the majority being identified for the first time in this matrix. Significant correlations were found between the opioid concentrations in hair and the administered medication doses, indicating that hair analysis may reflect the extent of opioid exposure in this population. Furthermore, metabolite ratios similar to the ones commonly found in adult hair were identified, which are forensically important to differentiate between active intake of a drug and contamination. The metabolite ratio of β‐hydroxyfentanyl to fentanyl was particularly well suited for children and neonatal patients. In conclusion, concentration ranges, metabolite ratios, and dose correlations of the studied opioids in pediatric hair were established, providing insights into opioid incorporation pathways.

This study investigated the incorporation of novel and traditional medically used opioids into the hair of 118 pediatric and neonatal patients. Concentrations (median [range]) in hair were as follows: fentanyl: 4.03 pg/mg [0.10–343], sufentanil: 0.31 pg/mg [0.10–8.64], remifentanil: 0.14 pg/mg [0.10–0.43], and morphine: 27.4 pg/mg [1.0–1870]. The results of this study will contribute to the interpretation of hair testing results in children and newborns and therefore play an important role in forensic toxicology.