Electrochemical Detection of Oxycodone and Its Main Metabolites with Nafion-Coated Single-Walled Carbon Nanotube Electrodes.

Oxycodone is a strong opioid frequently used as an analgesic. Although proven efficacious in the management of moderate to severe acute pain and cancer pain, use of oxycodone imposes a risk of adverse effects such as addiction, overdose, and death. Fast and accurate determination of oxycodone blood concentration would enable personalized dosing and monitoring of the analgesic as well as quick diagnostics of possible overdose in emergency care. However, in addition to the parent drug, several metabolites are always present in the blood after a dose of oxycodone, and to date, there is no electrochemical data available on any of these metabolites. In this paper, a single-walled carbon nanotube (SWCNT) electrode and a Nafion-coated SWCNT electrode were used, for the first time, to study the electrochemical behavior of oxycodone and its two main metabolites, noroxycodone and oxymorphone. Both electrode types could selectively detect oxycodone in the presence of noroxycodone and oxymorphone. However, we have previously shown that addition of a Nafion coating on top of the SWCNT electrode is essential for direct measurements in complex biological matrices. Thus, the Nafion/SWCNT electrode was further characterized and used for measuring clinically relevant concentrations of oxycodone in buffer solution. The limit of detection for oxycodone with the Nafion/SWCNT sensor was 85 nM, and the linear range was 0.5-10 µM in buffer solution. This study shows that the fabricated Nafion/SWCNT sensor has potential to be applied in clinical concentration measurements.

Predictive Value of Positive Drug Screening Results in an Urban Outpatient Population.

Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results. We analyzed the results of confirmatory assays in an outpatient setting to determine the predictive value of presumptive positive urine drug screen results using an automated immunoassay for eight common drugs or drug classes. Positive predictive values (PPVs), in descending order, were as follows: cannabinoids (100%), cocaine (100%), opiates (86.8%), benzodiazepines (74.6%), oxycodone (67.6%), methadone (44.1%) and amphetamines (9.3%). The number of positive barbiturate results was too small to be included in the statistical analysis.

Effects of filtration on the presence of particulate and oxycodone content of injections prepared from crushed OxyContin® tablets.

It is common for injecting drug users (IDU) to prepare injections by crushing tablets which are not designed for parental administration. The injection of insoluble tablet excipients can lead to serious local and systemic medical complications. The aim of the study was to investigate the effectiveness of various types of filters in removing harmful insoluble particles from the injections prepared using crushed oxycodone tablets. Injections were prepared from a sustained-release oxycodone tablet formulation. The filtration of tablet extracts was carried out following procedures used by IDU using makeshift filter and commercially available filters. Particulate contamination and oxycodone content were analysed using light microscopy and spectrophotometer. Unfiltered extracts contained hundreds of thousands of particles of sufficient size to cause harms. Cigarette filters removed large particles but failed to remove small particles. The combination of cigarette filter and syringe filter (0.45 µm or 0.22 µm) reduced the particle count by 90 - 95%. A double membrane syringe filter (0.8/0.2 µm) removed more than 99% of the particles. Recovery of oxycodone was more than 95% with the tested syringe filters. Particulate contamination in injections prepared from crushed tablets can be effectively removed using a combination process of cigarette filter and syringe filters, or a 0.8/0.2 µm syringe filter. Compared to other filters, the 0.8/0.2 µm syringe filter did not block, the filtration was quick and easy to perform, and did not retain oxycodone. The use of a 0.8/0.2 µm syringe filter can provide an important harm reduction measure for IDU.

Analysis of pharmaceutical compounds from glass, fabric, steel, and wood surfaces at atmospheric pressure using spatially resolved, nonresonant femtosecond laser vaporization electrospray mass spectrometry.

Laser electrospray mass spectrometry (LEMS) is demonstrated for pharmaceutical samples at atmospheric pressure. A nonresonant, femtosecond duration laser pulse vaporizes native samples at atmospheric pressure into an electrospray plume for ionization with subsequent transfer into a time-of-flight mass spectrometer. The active ingredients in pharmaceutical tablets were detected in the presence of binders and fillers in intact formulations using LEMS. Mass spectra were also obtained for microgram amounts of the pharmaceutical compounds loratadine, oxycodone, and atenolol deposited on glass, wood, steel, and polyester fabric. The neutral capture efficiency by the electrospray plume for nonresonant laser vaporization of oxycodone and atenolol desorbed from steel is 2.4% +/- 1.5% and 0.25% +/- 0.18%, respectively. LEMS imaging of the spatial distribution of an oxycodone spot on a metal slide with resolution of 250 mum is also presented.

Comparison of oxycodone in vitreous humor and blood using EMIT screening and gas chromatographic-mass spectrometric quantitation.

Vitreous humor may serve as a useful alternative specimen for oxycodone analysis in death investigations where blood samples are not available or are of poor quality or limited quantity. The purpose of this study was to investigate the relationship between immunoassay results and gas chromatography-mass spectrometry (GC-MS) quantitation of oxycodone in postmortem vitreous humor and blood. When used with vitreous humor calibrators, the Microgenics DRI Oxycodone (EMIT) Assay was found to be linear from 25 to 500 ng/mL with an limit of detection of 25 ng/mL. Vitreous humor and postmortem blood precipitate immunoassay responses in 57 oxycodone-positive cases were found to be correlated (r(2) = 0.69, p < 0.01). Confirmation and quantitation of oxycodone in vitreous humor by GC-MS was linear from 50 to 1000 ng/mL with a limit of detection of 10 ng/mL and a limit of quantitation of 50 ng/mL. In 30 cases, oxycodone vitreous humor concentrations ranged from less than 50 to 945 ng/mL, and blood concentrations ranged from 103 to 768 ng/mL. The average vitreous humor/blood ratio was 1.16 and ranged from 0.12 to 3.26. Disparities between vitreous fluid and blood oxycodone concentrations were seen in a few cases.

Determination of meperidine, tramadol and oxycodone in human oral fluid using solid phase extraction and gas chromatography-mass spectrometry.

Analytical procedures for the determination of meperidine, tramadol and oxycodone in oral fluid have been developed and validated using gas chromatography-mass spectrometry (GC/MS) following initial screening with enzyme linked immunosorbent assay (ELISA). The oral fluid samples were collected using the Quantisal device, and any drugs present were quantified using mixed mode solid-phase extraction and electron impact GC/MS. For confirmation, three ions were monitored and two ion ratios determined, which were within 20% of those of the known calibration standards. The limits of quantitation were 10 ng/mL; the intra-day precision of the assays (n=5) was 2.33%, 1.00% and 7.61%; inter-day precision 2.48%, 2.44% and 5.8% (n=10) for meperidine, tramadol and oxycodone, respectively. The percentage recovery of the drugs from the collection pads was 86.7%, 87.7% and 96.6%, respectively (n=6). The methods were applied to specimens obtained during research studies in the USA.

Stability indicating HPLC method for the estimation of oxycodone and lidocaine in rectal gel.

An HPLC method for the quantification of oxycodone and lidocaine in a gel matrix is described. The mobile phase consisted of methanol--water--acetic acid (35:15:1 v/v/v) and was delivered at 1.5 ml/min through a 4.6 x 250 mm Zorbax SB-C8 column. Oxycodone was detected at 285 nm and lidocaine at 264 nm. Linear calibration curves were obtained for oxycodone in the range of 0.05--1.5% (w/w) and for lidocaine in the range of 0.1--5.0% (w/w). Oxycodone and lidocaine were treated with hydrogen peroxide and the oxidation products were readily separated on the column. The method was applied to assess the stability of a gel containing oxycodone hydrochloride (0.3% w/w) and lidocaine (1.5% w/w). The gel was stored under refrigeration in ready-to-use syringes and under these conditions oxycodone and lidocaine were stable for at least 1 year. The gel is useful in the management of tenesmus in rectal cancer.

The routine analysis of breast milk for drugs of abuse in a clinical toxicology laboratory.

Drug screening of breast milk in a clinical toxicology laboratory is reported. Findings from three cases include cocaine, ethylbenzoylecgonine (cocaethylene), ethanol, oxycodone, codeine, and nicotine. We believe this to be the first report of ethylbenzoylecgonine in human breast milk. One other specimen submitted for analysis was screened with negative results. Screening and confirmation procedures adapted for use with breast milk are described. Finally, the potential for cocaine intoxication from mother to baby is discussed. Estimates of infant blood cocaine concentration are given which may increase awareness of the need to monitor milk and blood cocaine concentrations in the infant when the situation warrants.

A closer look at acetyl and pentafluoropropionyl derivatives for quantitative analysis of morphine and codeine by gas chromatography/mass spectrometry.

PFPA and acetic anhydride derivatives of morphine and codeine were evaluated with respect to stability, chromatography, potential for analytical interferences by other opiates, and suitability of major fragment ions for analysis by GC/MS with deuterated internal standards and selected ion monitoring (SIM). The PFPA derivatives showed acceptable stability and could be analyzed without interference from other opiates, but the codeine derivative had relatively poor chromatography and its mass spectrum had only two ions suitable for SIM. The acetic anhydride derivatives were stable and chromatographed well, but diacetyl hydromorphone enol, a minor product of derivatization of hydromorphone, interfered with analysis of morphine. 3-Monoacetylmorphine, a minor product of derivatization of morphine, prevented use of the abundant m/z 285 ion of derivatized D3-codeine as a qualifying ion in quantitative assays. The acetic anhydride derivative of morphine cannot be distinguished from the corresponding derivative of the heroin metabolite 6-monoacetylmorphine.