The use of liquid chromatography/mass spectrometry for quantitative analysis of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue

Abstract

Sensitive and reproducible methods for the determination of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue by liquid chromatography/mass spectrometry are described. Deuterated analogs of the substances were used as internal standards. Samples in Ringer solution were analyzed by direct injection of 10 microL Ringer solution diluted by an equal volume of water. The limit of quantification was 0.5 ng/mL and the method was linear in the range of 0.5-150 ng/mL for all substances. To analyze oxycodone and oxymorphone in rat plasma, 50 microL of plasma were precipitated with acetonitrile, and the supernatant was directly injected onto the column. To analyze oxycodone, oxymorphone and noroxycodone in rat plasma, 100 microL of rat plasma were subjected to a C18 solid-phase extraction (SPE) procedure, before reconstituting in mobile phase and injection onto the column. For both methods the limit of quantification in rat plasma was 0.5 ng/mL and the methods were linear in the range of 0.5-250 ng/mL for all substances. To analyze the content of oxycodone, oxymorphone and noroxycodone in rat brain tissue, 100 microL of the brain homogenate supernatant were subjected to a C18 SPE procedure. The limit of quantification of oxycodone was 20 ng/g brain, and for oxymorphone and noroxycodone 4 ng/g brain, and the method was linear in the range of 20-1000 ng/g brain for oxycodone and 4-1000 ng/g brain for oxymorphone and noroxycodone. All methods utilized a mobile phase of 5 mM ammonium acetate in 45% acetonitrile, and a SB-CN column was used for separation. The total run time of all methods was 9 min. The intra-day precision and accuracy were <11.3% and <+/-14.9%, respectively, and the inter-day precision and accuracy were <14.9% and <+/-6.5%, respectively, for all the concentrations and matrices described.

In Vivo Blood-Brain Barrier Transport of Oxycodone in the Rat: Indications for Active Influx and Implications for Pharmacokinetics/Pharmacodynamics

“…Each individual brain tissue sample was pretreated as described previously (Boström et al, 2004). The sample was homogenized with a 5-fold volume of 0.1 M perchloric acid.…”

“…Oxycodone and the microdialysis probe calibrator oxycodone-D3 were quantified using a liquid chromatography-tandem mass spectrometry method (Boström et al, 2004). Oxycodone-D6 was used as internal standard.…”

Oxycodone Pharmacokinetics and Pharmacodynamics in the Rat in the Presence of the P-Glycoprotein Inhibitor PSC833

“…11 In brief, 50 mL of plasma was precipitated with 100 mL of acetonitrile and vortexed for 5 s. After centrifugation at 10000 rpm for 5 min, 30 mL of the supernatant was injected onto the column.…”

An automated and fully validated LC‐MS/MS procedure for the simultaneous determination of 11 opioids used in palliative care, with 5 of their metabolites

“…Procedures found in the literature especially focus not only on the morphine-based opioids buprenorphine (BUP), 19 -27 codeine (COD) and morphine (MOR) 28 -38 itself but also on opioids like FEN, 39 -41 hydromorphone (HYD) 42 -44 or methadone (MET). 45 LC-MS methods for analysis of the other opioids of interest like oxycodone (OC), 31,46,47 oxymorphone (OM), 46 piritramide (PIR), 48,49 tilidine (TIL) and tramadol (TRA), 50 -52 and especially assays for the simultaneous determination of different opioids 53 are rarely described. Patients under palliative care often receive combinations of various opioids, e.g.…”