Neonatal Cord Tox Panel and Maternal Perinatal Fentanyl Exposure: A Retrospective Chart Review

Objective: The specific aim of this study was to determine if the currently available cutoff for fentanyl in umbilical cord (UC) was appropriate to distinguish illicit fentanyl exposure from therapeutic in-hospital administration of fentanyl. Study Design: Medical record review was conducted for perinatal administration of fentanyl and the detection of fentanyl in the corresponding routine UC toxicology. Specimens were initially tested with immunoassay followed by mass spectrometry (n = 62). Result: Excluding a single specimen that was confirmed positive, specimens were below the assays’ limit of quantification. The immunoassay’s mean b/b0 for the cases that received and did not receive fentanyl prior to delivery was 91.3% ± 10.6% and 98.2% ± 6.5%, respectively (p = 0.003). Conclusion: We demonstrated that UC is a suitable specimen type for the detection of fentanyl and that the cutoff selected adequately identifies illicit fentanyl use while not flagging cases where fentanyl was administered by the hospital prior to birth.

The Identification of Prenatal Exposure to Mitragynine Using Umbilical Cord Tissue

Objective: Kratom is widely available and literature exploring the effects of prenatal kratom exposure is lacking. This study aims to report a validated method for the detection of mitragynine in the umbilical cord and report our observations for specimens received at a national commercial reference laboratory. Study Design: Assays were validated according to the recommendations of ANSI/ASB. A retrospective evaluation of records at a national reference laboratory was conducted to determine prevalence and co-exposure to other substances of abuse. Result: Mitragynine was detected in 19 of 4456 specimens (0.43%) with concentrations ranging from 4 to >50 ng/g. Thirteen (13) of these specimens were positive for only mitragynine while the other 6 were also positive for either marijuana or opiates. Conclusion: Umbilical cord is a suitable specimen type for the surveillance of maternal kratom use and can be used to identify exposed neonates for further investigations into short- or long- term health consequences.

Liquid Chromatography-Tandem Mass Spectrometry Assay to Detect Ethyl Glucuronide in Human Fingernail: Comparison to Hair and Gender Differences

Over the past decade, the use of hair specimens for the long-term detection of the alcohol biomarker ethyl glucuronide has been increasing in popularity and usage. We evaluated the usefulness of fingernail clippings as a suitable alterna-tive to hair for ethyl glucuronide detection. A liquid chromatography-tandem mass spectrometry method for the detection of ethyl glucuronide in fingernail clippings was fully validated and used to analyze the hair and/or fingernail specimens of 606 college-aged study participants. The limit of detection was 2 pg/mg, the limit of quantitation was 8 pg/mg and the method was linear from 8 to 2000 pg/mg. Intra- and inter-assay imprecision studies at three different concentrations (20, 40, 200 pg/mg) were all within 7.8% and all intra- and inter-assay bias studies at these levels were within 115.1% of target concentration. Ethyl glucuronide levels in fingernail (mean = 29.1 ± 55.6 pg/mg) were higher than ethyl glucuronide levels in hair (mean = 9.48 ± 22.3 pg/mg) and a correlation of the matched pairs was observed (r = 0.552, P < 0.01, n = 529). Evaluating each gender separately revealed that the correlation of male fingernail to male hair was large and significant (r = 0.782, P < 0.01, n = 195) while female hair to female fingernail was small yet sig-nificant (r = 0.249, P < 0.01, n = 334). The study results demonstrated that fingernail may be a suitable alternative to hair for ethyl glucuronide detection and may be the preferred sample type due to the lack of a gender bias.

Using Umbilical Cord Tissue to Identify Prenatal Exposure to Fentanyl and Other Commonly Abused Drugs

Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.

The Detection of 1-Palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoethanol and Ethyl Glucuronide in Human Umbilical Cord

In utero exposure to ethanol continues to be a significant public health issue and neonatal healthcare professionals are in need of objective means to identify exposed newborns. The aim of this study was to fully validate two methods for the detection of two direct alcohol biomarkers, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPE) and ethyl glucuronide (EtG), in umbilical cord and apply the assays to a group of authentic specimens. The limits of detections were 2 and 1 ng/g for POPE and ETG and the limits of quantitation were 4 and 3 ng/g, respectively. Inter and intra-day precision and accuracy measurements were within 15%. The assays were applied to 308 authentic specimens where we detected POPE in five (1.6%) specimens and EtG in twelve (3.9%) specimens. The mean concentrations were 11.4 ng/g ± 9.4 ng/g and 127.2 ± 227.7 ng/g for POPE and EtG, respectively. This study suggested that umbilical cord was a suitable specimen type for the identification of newborns exposed to ethanol in the womb and the prevalence of POPE and EtG detected in umbilical cord were consistent with the prevalence of self-reported binge drinking reported by the National Birth Defect Prevention Study (NBDPS) and Behavioral Risk Factor Surveillance System (BRFSS). Further studies are required to fully describe the association between the observed concentrations of POPE and EtG in umbilical cord to the level of maternal consumption of ethanol.

The Detection of THCA Using 2-Dimensional Gas Chromatography-Tandem Mass Spectrometry in Human Fingernail Clippings: Method Validation and Comparison with Head Hair

Marijuana use as well as abuse is a significant public health and public safety concern in the United States and using hair to identify marijuana users and abusers has been gaining acceptance in a number of venues including workplace, court ordered, and substance abuse treatment monitoring. After the presentation of a fully validated 2-dimensional gas chromatography-tandem mass spectrometry method for the detection of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCA), the chief metabolite of the main psychoactive compound in marijuana, Δ9-tetrahydrocannabinol (THC), we evaluated the usefulness of fingernail clippings as an alternative specimen type to hair by the analysis of a set of 60 matched pairs of head hair and fingernail clippings. The limit of detection was 10 fg/mg, the limit of quantitation was 20 fg/mg, and the assay was linear from 20 fg/mg to 500 fg/mg. The intra- and inter-assay imprecision and bias studies at 4 different concentrations (50, 100, 500, and 1000 fg/mg) were acceptable where all % Target observations were within 16% of their expected concentrations and all %CV calculations were less than 13.5%. THCA was detectable in more fingernail specimens (53.3%) than hair specimens (46.7%) and the mean concentrations in nails were on average 4.9 times higher than in hair (1813 fg/mg and 364 fg/mg, respectively). The THCA concentrations in hair and nail were strongly associated (r = 0.974, P < 0.01, n = 60) and the association was significant. The study demonstrated that fingernail clippings are a suitable alternative specimen type to hair to monitor for marijuana use and abuse.

Long-Term Detection of Propofol Glucuronide in Urine Following Anesthetic Induction and Maintenance with Propofol

Propofol is the most commonly used compound for the intravenous induction and maintenance of anesthesia. Propofol addiction and abuse have become causes for concern in the healthcare community, especially among anesthesia and surgical professionals. The US Drug Enforcement Administration does not list propofol on any Schedules and most hospitals do not have inventory controls in place to prevent its misuse. Propofol is detectable in blood plasma as the parent compound for as much as 15 hours post-anesthesia. The metabolite propofol glucuronide (PPFG) has been detected in blood and urine as far out as 60 hours. Here we report the long-term renal excretion of PPFG in specimens from A) four participants following a 14-day course of orally ingested propofol dosing, and B) a female patient following anesthetic induction and 15 minutes’ maintenance with propofol. Urinary PPFG was measurable well above limits of quantitation up to 6 days following oral ingestion and 28 days post-anesthesia. We also present a third set of data evaluating the likelihood of passive exposure to aerosolized propofol in the surgical environment by analyzing the levels of urinary PPFG of healthcare workers following operating room work shifts. The results presented here demonstrate that quantitation of PPFG in urinary samples is an efficient method of long-term screening for propofol misuse and abuse.