Anodyne by Design; Measuring the Prevalence of Esoteric Designer Opioids in Pain Management Patients.

The recent increase in illicit opioids sold on the black market, cut into heroin and masqueraded as prescription pills prompts a significant public health concern. Most designer opioids possess unknown potencies and unknown pharmacokinetics and their unregulated, variable dosages lead to rashes of overdoses. Additionally, many of the designer opioids, especially the fentanyl analogs are significantly more potent than heroin. High-profile cases involving overdoses of U-47700 and carfentanil have been reported in the media; however, the true prevalence of these and other designer opioids is unknown. Independent LC-MS-MS screen and confirmation methods have been developed and validated to identify and quantify fentanyl, and 18 designer opioids and their metabolites; methods were then exercised on urine specimens from contract pain management clients. Assuming patients in a pain management program may have a higher probability to seek out self-medication, samples from pain management patients were investigated for designer opioids. Similarly, pain management patients identified as using heroin may be more likely to experiment with or be accidentally exposed to designer opioids, specimens screening positive for the heroin metabolite 6-acetylmorphine were specifically chosen for designer opioid screening. Within this small group of pain management and heroin-positive samples, nine designer opioids were detected at a total prevalence of 25%. When screening random pain management samples not positive for heroin, a considerably lower percentage of samples (<1%) were identified as positive for designer opioids. Furanyl fentanyl, fluorobutyryl fentanyl and acetylfentanyl were the most prevalent designer opioids detected in both test groups.

Profiting from Probability; Combining Low and High Probability Isotopes as a Tool Extending the Dynamic Range of an Assay Measuring Amphetamine and Methamphetamine in Urine.

A wide range of concentrations are frequently observed when measuring drugs of abuse in urine toxicology samples; this is especially true for amphetamine and methamphetamine. Routine liquid chromatography-tandem mass spectrometry confirmatory methods commonly anchored at a 50 ng/mL lower limit of quantitation can span approximately a 100-fold concentration range before regions of non-linearity are reached deteriorating accurate quantitation and qualitative assessments. In our experience, approximately a quarter of amphetamine and methamphetamine positive samples are above a 5,000 ng/mL upper limit of quantitation and thus require reanalysis with dilution for accurate quantitative and acceptable qualitative results. We present here the development of an analytical method capable of accurately quantifying samples with concentrations spanning several orders of magnitude without the need for sample dilution and reanalysis. For each analyte the major isotopes were monitored for analysis through the lower concentration ranges (50-5,000 ng/mL), and the naturally occurring, low probability 13C2 isotopes were monitored for the analysis of the high concentration samples (5,000-100,000 ng/mL amphetamine and 5,000-200,000 ng/mL methamphetamine). The method simultaneously monitors transitions for the molecules containing only 12C and 13C2 isotopologues eliminating the need for re-extraction and reanalysis of high concentration samples.

Analysis of total and transferrin-bound iron in human serum for pharmacokinetic studies of iron-sucrose formulations.

BACKGROUND: Patients with iron-deficiency anemia benefit from intravenous iron therapies. Development of these pharmaceutical agents requires pharmacokinetic studies monitoring levels of both the administered agent and transferrin-bound iron (TBI). Successful pharmacokinetic methods must discriminate iron species. RESULTS: Routine colorimetric procedures were used to reliably measure total iron and TBI following iron-sucrose administration. Iron was liberated from iron-sucrose allowing the determination of all circulating iron. Solid-phase sample processing allowed the measurement of TBI. Circulating iron-sucrose could then be calculated as the difference between total iron and TBI. CONCLUSION: A reproducible and robust spectrophotometric method was developed and validated for measuring total iron and TBI in human serum following iron-sucrose therapy.