Normorphine

Two independent lot numbers of certified reference standards of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, normorphine, hydromorphone as well as a single lot of the isotopically labeled internal standards (IS) morphine-d₃ morphine-3-β-glucuronide-d₃, morphine-6-β-glucuronide-d₃, and hydromorphone-d₆ were all purchased from Cerilliant Corporation (Round Rock, TX). Interference standards (see Supplemental Table 1) were obtained from Cerilliant Corporation. Drug-free serum was obtained from Bio-Rad Laboratories (Irvine, CA). High-performance liquid chromatography (HPLC) grade water and methanol were purchased from Fischer Scientific (Pittsburgh, PA) and formic acid was acquired from Sigma Aldrich (St. Louis, MO). For selectivity, matrix effects and endogenous studies, remnant human serum was acquired from vacutainer serum separator tubes (SST) (BD, Franklin Lakes, NJ) and plasma for the plasma to serum comparison from lithium heparin tubes (BD, Franklin Lakes, NJ) via an Institutional Review Board (IRB)-approved protocol through The Johns Hopkins University School of Medicine.