A partnership between the Center for Forensic Science Research and Education (CFSRE) and the Philadelphia Department of Public Health (PDPH) has been established to accurately assess the drug supply in Philadelphia, Pennsylvania, USA. This initiative was established as a comprehensive effort examining various drug materials and drug forms, in both qualitative and quantitative fashions. The information and results reported herein represent a subset of the drug supply and not its entirety.
Suggested Citation: Krotulski, AJ, Shinefeld, J, DeBord, J, Logan, BK (2022), Fentanyl Purity, Potency, & Synthesis: Real-Time Testing of Opioid Drug Products in the United States, Center for Forensic Science Research and Education, United States of America.
WHAT IS FENTANYL? Fentanyl is a synthetic opioid first synthesized in 1960. Fentanyl is used widely in medicine for the treatment of severe pain. Fentanyl is reported to be 50 to 100 times more potent than morphine. Like other opioids, fentanyl is a central nervous system depressant and in overdose scenarios can lead to a range of adverse effects, including sedation, respiratory depression, and in severe cases fatal overdose. The prevalence of fentanyl in the United States recreational drug supply has continued to increase since the mid-2000s, becoming the most frequently encountered opioid in the United States. Recreational fentanyl (sometimes referred to as illicitly manufactured fentanyl) is the primary synthetic opioid identified in fatal drug overdoses, although there are increasingly reports of fentanyl poly-drug occurrences (e.g., in combination with xylazine, benzodiazepine, stimulants). Recreational fentanyl is commonly ingested through various routes of administration, including injection, smoking, and ingestion. Fentanyl remains a drug of high public health concern among an increasingly volatile drug supply, and its prevalence has thus far only increased despite various countermeasures.
WHAT ARE PURITY AND POTENCY? Purity is defined as the amount or quantity of a specific drug in a material or product. Purity is assessed on an individual drug basis and can be reported as a percent (%) or absolute weight (mg). For example, the purity of a 100 mg powder might be 10% (or 10 mg) for fentanyl, 30% (30 mg) for xylazine, and 60% (60 mg) for mannitol (Figure 1). Potency is defined by the strength of effects the drug product can have in humans. Potency relates the purity of all pharmacologically active constituents. Purity vs. potency is best described by methamphetamine quantitative testing where purity is the amount of methamphetamine in a product and potency is more specifically the amount of d-methamphetamine. Herein relating to fentanyl, purity is the amount of fentanyl in a product while the Potency Index (Figure 3) represents the combined effects of all opioids, including drugs like heroin and para-fluorofentanyl. Potency index is calculated using relative pharmacological activity (EC50), normalized, and expressed on a scale where a fentanyl powder of 10% purity represents a baseline unit of 1.
DOWNLOAD THE FULL REPORT FOR THIS AND SO MUCH MORE!!!
Calculating Potency Index (PI)
The United States is in the midst of an overdose epidemic which is underlined by poly-drug use. Poly-drug combinations can be rooted in drug products containing, at times, more than one opioid. As quantitative drug purity data become available, scientists and public health officials need a comprehensive yet simple methodology to compare drug products. For this purpose, the potency index was developed. Potency index is a numeric value that takes into account the amount of a drug present (i.e., purity) and its relative potency, or potency factor (e.g., compared to fentanyl). The calculation is the sum of all similar pharmacologically active drugs present and is normalized to a comparator (e.g., fentanyl at 10% purity) for ease of understanding and utility. Potency index can be calculated for and applied to other drug classes, but herein is used as a representation of opioids.
Equation 1 can be applied to calculate Opioid Potency Index, where…
- PF is the Potency Factor compared to fentanyl and is calculated as EC50Opioid / EC50Fent at the mu opioid receptor.
- Examples of PFs: Fentanyl = 1, Heroin = 0.02, para-Fluorofentanyl = 0.33, ortho-Fluorofentanyl = 3, Carfentanil = 100.
- Purity is the amount of drug in a specified sample and is expressed as a percent (e.g., 10%, 23%).
- […] indicates that the numerator should be continued for all drugs (in this case opioids) present in the sample.
- The denominator is 10 — a Normalizing Factor applied so a sample of 10% fentanyl-only represents a Potency Index of 1.
- Potency Index is reported to one decimal place (e.g., 0.9, 4.6, etc.) until the value eclipses 10.
- Tolerance, dose, and other use factors are assumed to be constant at the individual level when assessing Potency Index; however, it should be understood that these factors will influence inter-individual outcomes.