In vivo pharmacokinetics of selective mu-opioid peptide agonists.
The mu opioid receptor agonist Tyr-D-Arg-Phe-Lys-Amide (D-Arg2-Lys4-Dermorphin(1-4)amide=DALDA) was infused continuously for 2 h into sheep. The presence of DALDA in ovine plasma was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and mass spectrometry (MS) in plasma samples that were obtained at different times during and following that infusion. A stable isotope-incorporated internal standard, deuterated DALDA (d5-DALDA), was used for the MS quantification of DALDA via the protonated molecule ion, (M+H)+, of DALDA and of d5-DALDA. Time-course data (microg DALDA ml(-1) plasma vs. time) were obtained. Tandem MS (MS-MS) provided the product-ion spectrum of the (M+H)+ ion of DALDA in one of the samples to confirm the amino acid sequence of DALDA.