Evaluation of Opioids and Metabolites in Hair and Sweat of Pediatric Patients in a Monitored Clinical Context, by Means of Targeted Liquid Chromatography-tandem Mass Spectrometry
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 13 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Obtained written informed-consent from legal representatives (and oral consent from the patient).
- •Patient's age must be within date of birth irrespective of gestational age to completed 13th year of life
- •Patients that received single or multiple treatment (either with single doses or continuous infusion) of fentanyl, remifentanil or sufentanil either during surgery or during stay in the pediatric intensive care unit
排除标准
- •Patient's age of 14 or older
- •Inability to understand the study procedure due to language or cognitive reasons (applies to legal representatives and elder children)
- •Denied or missing informed consent
- •Insufficient amount of head hair to obtain hair sample
- •Cosmetic hair treatment, like coloring, bleaching and dying
研究组 & 干预措施
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.
干预措施: Fentanyl (Drug)
结局指标
主要结局
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.
时间窗: Through study completion, an average of two years
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 Quad™ 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.
Evaluation of the opioid and metabolite concentrations (ng/mL: units of nanograms of opioid per milliliter) in the sweat extracts of the study population.
时间窗: Through study completion, an average of two years
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 Quad™ 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.
次要结局
- Normative opioid concetration values and metabolite reatios in pediatric hair.(after data evaluation, 3 months after end of study)