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Biomedical subjects

G B Baker

Publications and source records attributed to G B Baker.

231 records · Page 13Linked to original sources
PubMed1976

Procedural difficulties in the gas-liquid chromatographic assay of the arylalkylamines.

A gas-liquid chromatographic method for the estimation of 2-phenylethylamine in rat brain tissue is described. The procedure involves initial separation of the amine from homogenates with ion-exchange chromatography, subsequent acetylation of the eluate and extraction of the N-acetylated amine with ethyl acetate. The N-acetyl-2-phenylethylamine derivative is then converted to the pentafluoropropionyl derivative and quantitated with electron capture detection. Difficulties involved with alternative separative procedures and derivative formation are discussed.

Animals↗
PubMedDate not supplied

Urinary excretion of MHPG and normetanephrine in attention deficit hyperactivity disorder.

Twenty-four-hour excretion (expressed per gram of creatinine) of the norepinephrine metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NME) was measured in children with attention deficit hyperactivity disorder (ADHD) and in normal subjects matched for age and education. In contrast to findings with Tourette syndrome patients, in the ADHD patients there was no significant difference in excretion of MHPG and NME from control values.

Attention Deficit Disorder with Hyperactivity↗
PubMedDate not supplied

Para-hydroxytranylcypromine: presence in rat brain and heart following administration of tranylcypromine and an N-cyanoethyl analogue.

para-Hydroxytranylcypromine (p-OHTCP) has recently been unequivocally identified in our laboratory as a metabolite of the antidepressant tranylcypromine (TCP). In the study reported here, we have determined brain and heart levels of p-OHTCP in the rat after intraperitoneal administration of a 0.1 mmol/kg dose of TCP or N-(2-cyanoethyl)tranylcypromine (CE-TCP). The animals were killed at 5, 15, 30, 60, 120 or 240 min after drug administration and the tissues (brain and heart) rapidly dissected out. The tissues were frozen in isopentane on solid carbon dioxide and stored at -20 degrees C until time of analysis. Tissue levels of p-OHTCP, TCP and CE-TCP were determined after aqueous pentafluorobenzoylation by conducting analyses with a gas-liquid chromatograph equipped with a fused silica (SE-54) capillary column and an electron-capture detector. Our results show that substantial concentrations of p-OHTCP were present in both brain and heart after TCP and CE-TCP administration. Higher levels of p-OHTCP were present in the brain than in the heart after TCP treatment, but this situation was reversed with the CE-TCP-treated rats. Since p-OHTCP has been shown to retain some MAO-inhibiting properties and to have effects on uptake of catecholamines and serotonin it could therefore contribute to the pharmacological profile of TCP.

Animals↗
PubMedDate not supplied

A rapid electron-capture gas chromatographic procedure for the analysis of p-hydroxymephenytoin.

An electron-capture gas chromatographic procedure was developed for detection and quantification of p-hydroxymephenytoin (OHMEP), a metabolite of S-mephenytoin, in human liver microsomal preparations. OHMEP was derivatized with pentafluorobenzoyl chloride (PFBC) under basic aqueous conditions prior to analysis on a gas chromatograph equipped with a capillary column and an electron-capture detector. Dextrorophan was carried through the procedure as internal standard. The structure of the PFB derivative was confirmed using combined gas chromatography-mass spectrometry (GC-MS). The procedure is rapid and reproducible and produces a stable derivative that has excellent chromatographic properties. The limit of detection was less than 5 ng/ml, and the method was applied to extracts of human liver microsomes, which had been incubated with S-mephenytoin [a probe substrate for cytochrome P450 (CYP) 2C19].

Anticonvulsants↗
PubMedDate not supplied

A rapid high-pressure liquid chromatographic procedure for determination of flumazenil in plasma.

INTRODUCTION: Flumazenil antagonizes the effects of benzodiazepines at gamma-aminobutyric acid (GABA) type A receptors in the central nervous system. Flumazenil has been reported to provoke panic attacks in patients with panic disorder (PD) but not in healthy controls. A rapid high-pressure liquid chromatographic (HPLC) method was developed for determination of flumazenil in plasma samples from PD patients receiving flumazenil and the results obtained with that assay are reported here. METHODS: Samples from 37 PD subjects receiving 2 mg of flumazenil intravenously were analyzed. Extraction under basic conditions was followed by an HPLC assay with UV detection (250 nm). Lamotrigine was used as intermal standard and a standard curve was constructed for each assay run. Flumazenil concentrations were measured in all the subjects in samples collected at 2 and 4 min after the drug administration and in some subjects, measurements were also done in samples collected at 7.5, 15, 30, 45, and 60 min. RESULTS: The procedure was reproducible and linear (from 2.5 to 1000 ng/ml). At 2 and 4 min after flumazenil administration, the concentrations did not differ significantly between panicking and nonpanicking subjects, indicating that the pharmacokinetics of the drug is not the major determinant of the responses. There was a steep decline in the plasma concentration-time profile during the first 4 min, reflecting an extensive and rapid distribution after which the decline was slower. DISCUSSION: The method described here is rapid, replicable, and convenient for the determination of flumazenil in plasma.

Adult↗
PubMedDate not supplied

A rapid method of determining amphetamine in plasma samples using pentafluorobenzenesulfonyl chloride and electron-capture gas chromatography.

INTRODUCTION: Acute administration of (+)-amphetamine has been used as a model for mania in humans since it mimics the physiological, biochemical, and cognitive effects seen in mania. A rapid and sensitive method for the determination of amphetamine in human plasma samples using gas chromatography with electron-capture detection was developed in our laboratory to follow the time course of amphetamine levels in patients receiving this drug as part of a study using amphetamine as a model for mania. METHODS: Blood samples were taken from healthy male volunteers at 30, 60, 90, 150, 210, 240, and 480 min after administration of 25 mg of (+)-amphetamine. Plasma was isolated by centrifugation and used for the analysis. This method is a modification of the procedure described by Paetsch et al. [J. Chromatogr. 573 (1992) 313] for the determination of amphetamine in rat brain tissue. Amphetamine was derivatized under basic conditions using pentafluorobenzenesulfonyl chloride (PFBSC) prior to analysis on a gas chromatograph equipped with a capillary column and an electron-capture detector. The internal standard used was benzylamine. The structure of the amphetamine derivative was confirmed using combined gas chromatography-mass spectrometry (GC-MS). RESULTS: The limit of detection was <1 ng/ml, and the method was linear in the 1- to 100-ng range used. Mean amphetamine levels peaked at 3.5 h after drug administration, and were 40.8 +/- 1.5 ng/ml at that time. DISCUSSION: This procedure produces a stable derivative with excellent chromatographic properties and is both simple and reproducible.

Adolescent↗
PubMedDate not supplied

Anticonvulsant activities of 4-bromobenzaldehyde semicarbazone.

Some of the properties of 4-bromobenzaldehyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to peritoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of gamma-aminobutyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 microM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABAA receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.

Animals↗
PubMedDate not supplied

Metabolism of methoxyphenamine in vitro by a CYP2D6 microsomal preparation.

Metabolism of methoxyphenamine (MP) was conducted in vitro using commercially available microsomes prepared from human AHH-1 TK+/-cells in which CYP2D6 had been expressed. This study has confirmed the involvement of CYP2D6 in the metabolism of MP to O-desmethylmethoxyphenamine (ODMP) and 5-hydroxymethoxyphenamine (5HMP), but not to N-desmethylmethoxyphenamine. It has also revealed that CYP2D6 catalyzes the formation of another, hitherto unknown, ring-hydroxylated metabolite of MP, isomeric with 5HMP. The analytical procedure used to identify and quantify MP metabolites involved an acetylation procedure that had distinct advantages. MP and its basic and amphoteric metabolites were all converted to neutral products that were efficiently extracted into organic solvent. The acetylated products also had good chromatographic properties and provided mass spectra that were readily interpretable. MP metabolism studies were also conducted with CYP2D6 microsomes in the presence of quinidine and quinine. The former was the more potent inhibitor of CYP2D6-catalyzed oxidations of MP. Its inclusion resulted in complete inhibition of metabolism of MP to ODMP, 5HMP, and its novel isomer. This study shows that the in vitro use of human cytochrome P450 isozyme preparations in drug metabolism studies can aid in the identification of possible in vivo metabolites of these drugs in humans and can provide information on putative drug-drug interactions.

Acetylation↗