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| Name | Class |
|---|---|
| University Children's Hospital, Zurich | OTHER |
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Hair analysis is a well-established and important tool in both forensic and clinical context. When it comes to the interpretation of positive hair analysis results, reliable and comprehensive reference data is essential. Such data on opioids, especially novel synthetic ones (such as fentanyl and its analogues (fentalogs)) is currently highly limited. This applies especially to hair with pediatric origin, due to differences in the metabolism and hair anatomy in children compared to adults.
Investigators hypothesize that opioids, both traditional and novel synthetic ones exhibit detectable concentrations and distinct metabolite ratios within the hair matrices of pediatric patients. Thus, this observational, prospective research study provides 150 hair and sweat samples from children who received opioids as part of surgery or pain management. The samples will be consecutively extracted and analyzed using a sensitive targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, enabling the quantitative determination of the opioid and metabolite concentrations. The study thereby contributes valuable reference data for both forensic and clinical applications, addressing challenges in interpreting hair analysis results in especially pediatric populations. Further, a deeper understanding of the mechanisms (e.g. via sweat) and pharmacokinetic processes involved in the opioid incorporation to hair will be achieved. The study has received ethical approval from the Swiss Ethics Board (approval number: 2022-01693 / amendment approval date: 09.01.2024).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KISPI 000 | Patients of the group received one or multiple clinically approved opioids, namely; Fentanyl, Remifentanil, Sufentanil, Alfentanil, Oxycodone, Morphine, Nalbuphine, Hydromorphone and Methadon. The drugs were administered in the course of a surgery or for pain management. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl | Drug | The drugs were administered in the course of a surgery or for pain management. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of the opioid and metabolite concentrations (pg/mg: units of picograms of opioid per milligram hair) in the hair samples of the study population. | For the collected hair samples, a two-stage extraction is performed, using methanol and a buffered methanol-water mixture for 90 minutes each. The extracts are then evaporated, resuspended in a 3:7 mixture of methanol and eluent A (20 mM ammonium formate with 0.1% (v/v) formic acid in water). The hair sample extracts will then be measured on an the LC-MS/MS system (SCIEX Triple Quadâ„¢ 7500 LC-MS/MS (QTRAP) System). A validated analysis method will be used for the analysis of the following opiates, opioids or their metabolites: hydromorphone, 4-ANPP, acetylcodeine, acetylmorphine, alfenanil, betahydroxyfentanyl, codeine, dihydrocodeine, fentanyl, hydrocodone, methadone, morphine, naloxone, norfentanyl, norsufentanil, omegahydroxyfentanyl, oxycodone, oxymorphone, pethidine, remifentanil, remifentanil-acid, sufentanil and tramadol. The data is processed with the software SciexOS version 1.6.7. | Through study completion, an average of two years |
| Evaluation of the opioid and metabolite concentrations (ng/mL: units of nanograms of opioid per milliliter) in the sweat extracts of the study population. | The extraction procedure of the sweat swabs looks as follows: the cotton ends of the forensic swabs will be cut and extracted with methanol. The methanol extracts will then be diluted to avoid detector saturation and mixed in a 3:7 ratio with eluent A. The sweat sample extracts will then be measured on an the LC-MS/MS system (SCIEX Triple Quadâ„¢ 7500 LC-MS/MS (QTRAP) System). A validated analysis method will be used for the analysis of the following opiates, opioids or their metabolites: hydromorphone, 4-ANPP, acetylcodeine, acetylmorphine, alfenanil, betahydroxyfentanyl, codeine, dihydrocodeine, fentanyl, hydrocodone, methadone, morphine, naloxone, norfentanyl, norsufentanil, omegahydroxyfentanyl, oxycodone, oxymorphone, pethidine, remifentanil, remifentanil-acid, sufentanil and tramadol. The data is processed with the software SciexOS version 1.6.7. | Through study completion, an average of two years |
| Measure | Description | Time Frame |
|---|---|---|
| Normative opioid concetration values and metabolite reatios in pediatric hair. | This data will be analyzed by using descriptive statistics (box plots) including the median, mean, 10th percentile, and 90th percentile values and for their distribution (normal or non-normal) by Shapiro-Wilks Test. Thus, opioid specific concentration values and metabolite ratios in hair of children will be established. |
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Inclusion Criteria:
Exclusion Criteria:
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The study population consists of patients (newborns, infants, children and adolescents up to 13 years of age) from the pediatric intensive care unit from the Children's Hospital Zurich. Patients in focus are exposed to fentanyl and fentalogs (remifentanil, sufentanil and alfentanil) or other more traditional opioids (such as morphine, oxycodone and methadone) either during surgery or as part of post-operative pain management for up to three months prior to study inclusion.
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| Name | Affiliation | Role |
|---|---|---|
| Tina Binz | University Zürich | Principal Investigator |
| Florian Zapf, Dr. | University's Children Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University's Children Hospital | Zurich | Canton of Zurich | 8032 | Switzerland |
The outcomes of the research will be published in peer-reviewed journals. Data will be strictly anonymized.
starting after publication
upon request via e-mail
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| D000077208 | Remifentanil |
| D017409 | Sufentanil |
| D004091 | Hydromorphone |
| D010098 | Oxycodone |
| D009020 | Morphine |
| D015760 | Alfentanil |
| D009266 | Nalbuphine |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011422 | Propionates |
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Hair samples (without hair root) Sweat Samples
| after data evaluation, 3 months after end of study |
| D000144 |
| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D003061 | Codeine |