Determination of nomifensine by a sensitive radioimmunoassay.

Abstract

1. A radioimmunoassay (RIA) has been developed for determination of both nomifensine and total nomifensine (nomifensine + conjugated nomifensine) in serum, plasma, and urine. 2. Antibodies were prepared in rabbits by immunization with N‐(8‐Nomifensine) succinamic acid‐ bovine serum albumin. 3H‐labelled drug was used as tracer. Separation of free from antibody‐bound nomifensine was carried out using dextran‐ coated charcoal. For determination of total nomifensine, the acid‐ labile conjugate was split by acidification. 3. The limit of detection for nomifensine is 300 pg/ml plasma and the cross‐reactivity of the metabolites is less that 1%. The influence of conjugated nomifensine on the results of nomifensine can be corrected. 4. Pharmacokinetics of nomifensine were determined in healthy volunteers after oral administration of 100 mg 14C‐labelled drug. Peak levels of 14C radioactivity (2,150 ng/ml), total nomifensine (1,252 ng/ml) and nomifensine (53 ng/ml) appeared within 1.5‐2 h; the half‐life of elimination from plasma was 1.5‐2 hours. The advantages of this routine method are high sensitivity, the requirement of small amounts of plasma, and simple handling.

Determination of nomifensine plasma concentrations: a comparison of radioimmunoassay and gas chromatography.

“…(ii) Radioimmunoassay A radioimmunoassay (RIA) based on the method of Heptner et al (1977), was evaluated for the determination of plasma concentrations of nomifensine.…”

“…The gas chromatographic method of Bailey, Fenoughty & Richardson (1977) and the radioimmunoassay of Heptner et al (1977) appear to be the most reliable techniques for nomifensine plasma. concentration determination.…”

Plasma Nomifensine Concentration

“…This observation may not be generally applicable as only a small patient population was investigated. Further pharmaco kinetic studies have shown the half-life of nomifensine to be 2-4 h [Heptner et al, 1977, McIntyre et al, 1981b, indicating that there should be a wide vari ation of plasma concentration within 1 day. Within day variation of plasma nomifensine concentrations was assessed in a female 31-year-old patient (No.…”

“…This method of collection and storage was found to be necessary in order to prevent significant degradation of the nomifensine samples [McIntyre et al, 1981a]. The analysis of unconjugated nomifensine and total nomifensine (unconjugated plus an acid-labile N-glucuronide conjugate) [see Heptner et al, 1978] was performed by radio immunoassay [Heptner et al, 1977]. The original assay technique was improved by a simple one-step extraction of plasma samples prior to unconjugated nomifensine determination [unpublished data].…”

A simple gas chromatographic method for the determination of nomifensine in plasma and a comparison of the method with other available techniques.

“…Not only does this give information on the kinetics of the drug, and therefore a greater appreciation of onset of action, dosage schedules, and so on, but a good analytical method is often a requirement for registration authorities. A number of methods have now been described in the literature for the measurement of nomifensine in plasma (Bailey et al, 1977;Heptner et al, 1977a;Vereczkey et al, 1976;Uihlein & Hajdu, 1977). In this paper we describe a simple and rapid gas chromatographic technique for the determination of plasma levels of nomifensine.…”