Automated capillary GC/NPD assay for the determination in plasma of McN-5707, a potential antidepressant drug
McN-5707 x HBr (trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexa-hydropyrrolo(2,1-a)isoquinoline hydrobromide (1:1)) is a novel, potential antidepressant which is currently under pre-clinical evaluation. The present study reports the development of a sensitive and reproducible capillary gas chromatographic (GC) assay with nitrogen-phosphorus ionization detection (NPD) for McN-5707 in plasma. The assay includes a three step extraction as follows: McN-5707 and the internal standard (IS) are extracted from alkalinized plasma (1 mL) into hexane and back-extracted into 0.1 N HCl. Following alkalinization of the aqueous layer, McN-5707 and IS are re-extracted into hexane. The solvent is evaporated and the residue is reconstituted with 50 ..mu..L of a solution of 10% methanol in toluene. A 2.5 ..mu..L aliquot is injected into an HP 5880A capillary GC using the HP 7672A auto-sampler. Separation is accomplished using a 15 m x 0.32 mm i.d. DB-5 fused silica capillary column and temperature programming from 160 to 200/sup 0/C at 10/sup 0//min. Calibration curves are linear from 1 to 100 ng/mL. Accuracy and precision, expressed as relative deviation from the true value and coefficient of variation are < 10% at all concentrations in the linear range. The assay has been successfully used for pharmacokinetic studies in rats and dogs and has been cross-validated with a /sup 3/H-norepinephrine uptake inhibition assay.
- Research Organization:
- McNeil Pharmaceutical, Spring House, PA
- OSTI ID:
- 5386303
- Report Number(s):
- CONF-8604222-; TRN: 86-026526
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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ANTIDEPRESSANTS
BIOASSAY
BIOCHEMICAL REACTION KINETICS
BLOOD PLASMA
DOGS
GAS CHROMATOGRAPHY
NORADRENALINE
RATS
SOLVENT EXTRACTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
CHROMATOGRAPHY
DRUGS
EXTRACTION
HORMONES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NEUROREGULATORS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques