Combined liquid chromatography–coulometric detection and microextraction by packed sorbent for the plasma analysis of long acting opioids in heroin addicted patients

The sublingual combination of buprenorphine and naloxone (Suboxone®) and Methadone Maintenance Therapy have been found effective in treating heroin addiction. A new analytical method suitable for the simultaneous determination of buprenorphine, norbuprenorphine, methadone and naloxone in human plasma by means of liquid chromatography with coulometric detection has been developed. The chromatographic separation was achieved with a phosphate buffer–acetonitrile mixture as the mobile phase on a cyano column. The monitoring cell of the coulometric detector was set at an oxidation potential of +0.600 V. A rapid clean-up procedure of the biological samples using a microextraction by packed sorbent technique has been implemented, employing a C8 sorbent inserted into a syringe needle. The extraction yield values were satisfactory for all analytes (>85%). The calibration curves were linear over a range of 0.25–20.0 ng mL−1 for buprenorphine and norbuprenorphine, 3.0–1000.0 ng mL−1 for methadone and 0.13–10.0 ng mL−1 for naloxone. The sensitivity was also high with limits of detection of 0.08 ng mL−1 for both buprenorphine and norbuprenorphine, 0.9 ng mL−1 for methadone and 0.04 ng mL−1 for naloxone. The intraday and interday precision data were always satisfactory.The method was successfully applied to plasma samples obtained from former heroin addicts treated with opioid replacement therapy.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We developed a combined HPLC method–microextraction by packed sorbent procedure. ► Coulometric detection was used for the first time. ► We examined long-acting opioids in plasma from former heroin addicts. ► MEPS approach reduced time analysis and sample and organic solvent consumption.