Determination of MDL 74,405, a synthetic analogue of α-tocopherol, in dog plasma and heart tissue by high-performance liquid chromatography with electrochemical detection

• Published in: Journal of chromatography. B, Biomedical applications Biomedical applications, 1994-06, Vol.656 (2), p.359-365
• Main Authors: Chan, Kenneth Y., Dusterhoft, Donald A., Chen, Teng-Man
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biological and medical sciences; Chromatography, High Pressure Liquid; Dogs; Electrochemistry; Free Radical Scavengers - analysis; Free Radical Scavengers - blood; General pharmacology; Medical sciences; Myocardium - chemistry; Pharmacology. Drug treatments; Stereoisomerism; Vitamin E - analogs & derivatives; Vitamin E - analysis; Vitamin E - blood
• ISSN: 0378-4347; 1572-6495
• DOI: 10.1016/0378-4347(94)00120-0

A high-performance liquid chromatographic (HPLC) procedure with electrochemical detection was developed to analyze MDL 74,405 (I), the (−)-( S)-enantiomer of an α-tocopherol analogue, in dog plasma and heart tissue after infusion (0.3 mg/kg/h). The sample preparation involved the addition of an internal standard to either the dog plasma and heart tissue prior to protein precipitation. After centrifugation, the resulting supernatant was directly analyzed by HPLC with a Zorbax Rx C 8 column and a mobile phase of acetonitrile—0.04 M potassium phosphate, pH 7.0 (70:30, v/v). The concentration of I found was ca. 100 ng/ml in plasma and ca. 3 μg/g in heart tissue. A chiral separation with an Ultron ES-OVM column and a mobile phase of methanol—0.025 M potassium phosphate, pH 6.5 (17:83, v/v) was also used to investigate the enantiomeric conversion of I. Preliminary results of a probe study indicated that I is not invested to the (+)-( R)-enantiomer in vivo.