Due to macroeconomic factors, the pharmaceutical industry has progressively outsourced larger amounts of its internal research efforts. One such example is the purchase of large volumes of control nonhuman primate (nhp) plasma from external vendors. During the bioanalysis of plasma samples collected during a Cynomolgus monkey PK study with racemic (±) ketamine, it was discovered that the vendor control nhp plasma used for standard curve samples contained ketamine (32 µM). This ketamine concentration correlated to an anesthetic dose of ketamine (10-15 mg/kg, IM), which was not cited in the vendor's plasma harvesting protocol. This study evaluated the effect of ketamine in control nhp plasma on the in vitro-derived unbound plasma fraction of small molecules, which would cause erroneous nhp efficacy and safety values.