Published: Journal of Analytical Toxicology, Volume 21, Number 4, July/August 1997, pp. 252–257.

Determination of Naltrexone and 6-b-Naltrexol in Plasma by Solid-Phase Extraction and Gas Chromatography–Negative Ion Chemical Ionization-Mass Spectrometry
W. Huang, D.E. Moody, R.L. Foltz, and S.L. Walsh

Solid-phase extraction (SPE) and a one-step derivatization are combined with gas chromatography–negative ion chemical ionization-mass spectrometry to simplify a previously reported method for the determination of naltrexone and its metabolite, 6-b-naltrexol, in human plasma. Deuterated isotopomers of naltrexone and 6-b-naltrexol are used as internal standards. After SPE, the extracts are derivatized with pentafluoropropionic anhydride at room temperature to form predominantly the bis-pentafluoropropionyl derivative of naltrexone and the tris-pentafluoropropionyl derivative of 6-b-naltrexol. The derivatized extracts are analyzed by monitoring ion currents at m/z 633 (naltrexone), m/z 636 (naltrexone-²H₃), m/z 633 6-b-naltrexol), and m/z 640 (6-b-naltrexol-²H₇). Control plasma samples containing 0.3, 3, or 30 ng/mL of each analyte were analyzed for precision and accuracy with the following results: intra-assay, the percentage of target concentrations were 107–113% for naltrexone and 107–120% for 6-b-naltrexol, and the coefficients of variation (CVs) were 3.1–6.3% for naltrexone and 3.1–5.7% for 6-b-naltrexol; interassay, the percentage of target concentrations were 103–110% for naltrexone and 110–113% for 6-b-naltrexol, and the CVs were 6.1–9.1% for naltrexone and 5.9–9.1% for 6-b-naltrexol. At the limit of quantitation (LOQ) of 0.1 ng/mL, both analytes quantitated within 20% of the target concentration with CVs less than 17%. The extraction recoveries determined at 0.3 and 30 ng/mL were 79 and 80% for naltrexone and 76 and 75% for 6-b-naltrexol. Bench-top stability tested with concentrations of 0.3 and 3.0 ng/mL did not decrease more than 10% from the zero-hour controls at 3, 6, and 24 h. Selectivity was determined using plasma from six donors and none showed interfering peaks greater than 22% of the LOQ for naltrexone and 53% of the LOQ for 6-b-naltrexol. Using this method, naltrexone and 6-b-naltrexol were readily detected in plasma specimens collected 5.5 h after oral doses of 25 or 100 mg naltrexone. Following discontinuation of treatment, naltrexone was detected 30 h after the 100-mg dose, whereas 6-b-naltrexol was detected 125 h after both the 25- and 100-mg doses.

Reproduction of editorial content of this journal is prohibited without publisher’s permission.

| Subscribe | Current Issue | Back Issues | Search | Advertise | Other Publications |