An automated, highly sensitive LC-MS/MS assay for the quantification of the opiate antagonist naltrexone and its major metabolite 6β-naltrexol in dog and human plasma

To support animal studies and clinical pharmacokinetic trials, we developed and validated an automated, specific and highly sensitive LC-MS/MS method for the quantification of naltrexone and 6β-naltrexol in the same run. In human plasma, the assay had a lower limit of quantitation of only 5 pg/mL. This was of critical importance to follow naltrexone pharmacokinetics during its terminal elimination phase. The assay had the following key performance characteristics for naltrexone in human plasma: range of reliable quantification: 0.005–100 ng/mL (r2 > 0.99), inter-day accuracy (0.03 ng/mL): 103.7% and inter-day precision: 10.1%. There were no ion suppression, matrix interferences or carry-over.