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Biomedical subjects

E H Taylor

Publications and source records attributed to E H Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1987

Total and free disopyramide by fluorescence polarization immunoassay and relationship between free fraction and alpha-1 acid glycoprotein.

Disopyramide is an antiarrhythmic drug with concentration dependent protein binding within the therapeutic range. We found good agreement between fluorescence polarization immunoassay (FPIA, Abbott TDX) and high performance liquid chromatography (HPLC) for total disopyramide among 27 admission patients' sera (FPIA = 1.12 (HPLC) -0.002, r = 0.982, SEE = 0.378 mg/l). Agreement between FPIA and HPLC for free disopyramide was similarly good (FPIA = 0.867 (HPLC) -0.003, r = 0.986, SEE = 0.09 mg/l, n = 27). Serum alpha 1 acid glycoprotein concentration (AAG) and free fraction (FF) percent of disopyramide correlated inversely (FF = -0.0112 (AAG) + 31.3 r = 0.707, SEE = 6.41 mg/l, n = 24), and the free disopyramide fraction varied greatly. For two pooled sera with 12 different disopyramide concentrations (range from 0.5-20.0 mg/l), the proportion of free fraction ranged from 6.5 to 73.2%. Overall, we found the free disopyramide fraction variable with each individual, total drug, and protein concentration. Therefore, free drug concentration should be monitored in disopyramide therapy, and FPIA is reliable for free as well as total drug assay.

Chromatography, High Pressure Liquid↗
PubMed1986

Rapid sample preparation and high performance liquid chromatographic determination of total and unbound serum disopyramide.

A rapid sample preparation procedure, which requires no solvent extraction or concentration, for the high performance liquid chromatographic (HPLC) determination of disopyramide is described. The chromatography is performed on a C-18 radial compression mu-Bondapak column and detection by absorbance at 254 nm with a run time of 12 min. The mobile phase is 10 mM sodium acetate (pH 4.5)/acetonitrile (3:1 vol/vol). For the total drug assay, 50 microliter 30% (wt/vol) trichloroacetic acid is added to 500 microliter serum, which causes the precipitation of protein. Following centrifugation, 100 microliter of supernatant is mixed with 25 microliters of internal standard (25 micrograms/ml, ethyl p-aminobenzoate), and 50 microliters of this mixture is injected into the HPLC. Unbound disopyramide is separated from protein-bound drug by filtration with an Amicon Centrifree filter, which removes 99.6% of protein and does not retain disopyramide. To 100 microliters of this filtrate is added 25 microliters of internal standard, and 50 microliters is injected into the HPLC. The assay is linear to at least 20 micrograms/ml. The total drug assay shows an average recovery of 93.0% with an average coefficient of variation (CV) of 3.4%. The unbound drug assay shows an average CV of 4.1%. The percentage of free drug in a sample containing 4.85 g/dl protein varies from 68.0 to 83.5% at concentrations of 2.5-10 micrograms/ml, which illustrates the concentration-dependent nature of the protein binding, and the need to measure the unbound fraction of drug. Of 31 drugs tested for interference, none was found to interfere.

Chromatography, High Pressure Liquid↗
PubMed1985

Serum osmolality in acute intoxication: a prospective clinical study.

The authors prospectively performed simultaneous determinations of serum delta osmolality (delta-Osm), enzymic (alcohol dehydrogenase [ADH]) quantitation of serum ethanol (EtOH), and urine drug screens on 339 acutely intoxicated patients. In addition, the authors established reference ranges for measured and calculated serum osmolalities in a group of 55 healthy volunteers. The authors determined the clinical utility of the combined delta-Osm/ADH procedure for detecting the presence of EtOH or other low molecular weight (Mr) volatiles. In the reference population, the measured osmolality (M-Osm) and calculated osmolality (C-Osm) was 285.1 +/- 4.3 (SD) mOsm/kg and 287.4 +/- 5.1 (SD) mOsm/kg, respectively. The correlation between delta-OsM and serum EtOH was 0.968 in 151 patients in whom EtOH was detected. The presence of drugs in 67 (44%) patients or absence of drugs in 84 (55.6%) patients was shown to have no significant effect on the delta-Osm. The delta-Osm/ADH method failed to detect a volatile other than EtOH in only two cases (0.6%) or in addition to EtOH in three cases (0.9%). The concentrations of these volatiles were not clinically significant. The sensitivity for detecting EtOH by means of the delta-Osm calculation was 98.1% with a specificity of 98.2%. A disparity (delta-Osm greater than 10 mOsm/kg) between delta-Osm and the EtOH determination suggested a volatile other than EtOH in five cases (1.5%), which was confirmed by head-space gas chromatographic (GC-HS) analysis. A volatile in addition to EtOH in seven cases (2.1%) was suggested but not confirmed by GC-HS analysis. The delta-Osm/ADH procedure provides an efficient, rapid, and readily available method to evaluate the acutely intoxicated patient for the presence of EtOH and/or other low Mr volatiles.

Adult↗
PubMed1984

Automated extraction and high-performance liquid chromatographic determination of serum clonazepam.

We have developed a rapid extraction process using the DuPont Prep I automated extractor/concentrator to prepare serum samples for the high-performance liquid chromatographic (HPLC) determination of clonazepam. The drug, at an alkaline pH, is applied to a styrene divinylbenzene preparatory extraction column. The Prep I is a reversible centrifuge that allows the sample to pass through the preparatory column, followed by a wash solution of deionized water. The rotor then reverses direction and dispenses 20 ml of ethyl acetate, which elutes the adsorbed drug into an aluminum cup that is automatically dried at 68 degrees C. The extract is reconstituted with 100 microliters of mobile-phase, 50-mM sodium acetate (pH 5.4):acetonitrile:methanol (450:235:265, vol/vol). The chromatography is performed on a C-18 radial compression cartridge and detection is by absorbance at 313 nm. A plot of peak height ratio against concentration is linear to at least 160 ng/ml. The recovery of clonazepam with this automated extraction is 97.5%, compared with 90.0% for a manual extraction method. The coefficient of variation is 2.9% with the automated extraction. Only propranolol was found to interfere with clonazepam, whereas clorazepate interferes with the elution of the internal standard, nordiazepam.

Autoanalysis↗
PubMed1983

Effect of experimental hyperphenylalaninemia on biogenic amine synthesis at later stages of brain development.

The effects of experimental hyperphenylalaninemia on catecholamine and serotonin synthesis in brain at a later stage of brain development were investigated. A group of 35-day-old rats treated with normal chow supplemented with 5% Phe + 0.4% alpha-methylphenylalanine, alpha MP, for the previous 10 days showed decreases in dopa, norepinephrine, and epinephrine versus controls. A group treated with a normal diet supplemented with 0.4% alpha MP showed similar decreases and these differences could be attributed to the presence of the phenylalanine hydroxylase and tyrosine hydroxylase inhibitor, alpha MP, rather than the hyperphenylalaninemia condition. No differences in dopamine were observed. Serotonin and 5-hydroxyindoleacetic acid (5HIAA) were decreased 50% in the HyPhe condition and were unaffected in the presence of alpha MP alone, indicating that the decreases in serotonin and 5HIAA were due to the increases in phenylalanine rather than the presence of the inhibitor. These abnormalities in serotonin metabolism at later stages of brain development may be relevant to early discontinuation of dietary therapy in the PKU patient and implies a role in tryptophan supplementation to increase intracerebral serotonin values.

Animals↗
PubMed1983

Effect of experimental hyperphenylalaninemia on myelin metabolism at later stages of brain development.

Myelination is the most important process in postnatal maturation of the nervous system and during this period the growing infant passes through a "vulnerable period" during which irreversible brain damage can occur if the neonate is subjected to a potential neurotoxin. This study was undertaken to investigate the mechanisms by which chronic hyperphenylalaninemia interferes with myelin metabolism, beyond the neonatal period of rapid myelination, at a time when myelin continues to accumulate. Rats of 25 days of age were placed on a hyperphenylalanimenia (HyPhe) inducing diet of 5% phenylalanine plus 0.4% alpha-methylphenylalanine (alpha MP) at 25 days of age to approximate plasma phenylalanine levels of an untreated human PKU patient (1.5 mM). The HyPhe group exhibited approximately a 15% decrease in the amount of myelin protein throughout the 70 days of the study. The rate of incorporation of 3H-lysine into both TCA precipitable whole brain proteins or myelin proteins did not vary from the HyPhe group and a weight matched control group (WMC). Therefore, this loss of myelin could not be attributed to a hypo-myelination. The turnover of whole brain proteins also was unaffected by the HyPhe treatment; however, the turnover of myelin proteins in the HyPhe group was dramatically different (t 1/2 = 3 days) from that of the WMC group (t 1/2 = 36 days) or a group treated with only alpha MP (t 1/2 = 26 days).

Amino Acids↗
PubMed1982

Turnover of the fast components of myelin and myelin proteins in experimental hyperphenylalaninaemia. Relevance to termination of dietary treatment in human phenylketonuria.

The turnover of myelin and of myelin protein fractions has been measured in the central nervous system of rats who were placed on a hyperphenylalaninaemia-inducing diet (3% L-phenylalanine and 0.12% p-chlorophenylalanine added to the normal laboratory chow) when they were 25 days of age. A considerably increased turnover of the fast component of myelin and of myelin protein fractions was observed, which was not found in weight-matched controls or in controls fed the normal laboratory chow supplemented with 0.12% p-chlorophenylalanine. The increased turnover is therefore due to the hyperphenylalaninaemic condition and not due to the slow-down in growth or the presence of p-chlorophenylalanine. Furthermore, an inhibition of myelin synthesis due to the hyperphenylalaninaemic condition has been observed. Since these effects on myelin metabolism can be demonstrated to occur even when the brain has matured considerably, prudence should be exercised in considering the termination of the dietary treatment of patients with phenylketonuria.

Amino Acid Metabolism, Inborn Errors↗
PubMed1975

Microbial transformation of aspidospermine.

Thirty actinomycetes were isolated from soil samples and screened for their ability to modify the structure of aspidospermine. One actinomycete culture converted aspidospermine into O-demethylaspidospermine but failed to modify N-deacetylaspidospermine, N-ethyl-N-deacetylaspidospermine, 7-methoxyindole, and 7-methoxytryptophan.

Actinomycetales↗
PubMedDate not supplied

Comparison of derivatives for determination of codeine and morphine by gas chromatography/mass spectrometry.

Pentafluoropropionic anhydride (PFPA) and heptafluorobutyric anhydride (HFBA) derivatives of morphine and codeine demonstrated poor spectra due to low abundances of secondary and tertiary ions. Trifluoroacetamide (MBTFA) has been a widely used derivative; however, the internal standard, nalorphine, displayed very poor stability and this resulted in split peaks by gas chromatography making MBTFA unsuitable for quantitative methods. Quantitation of codeine and morphine using bis-trimethylsilyltrifluoroacetamide (BSTFA/1%TMS) revealed a significant gradual decrease (p less than 0.05) of peak area ratio (PAR) of codeine and morphine compared to the internal standard using selected ion monitoring (SIM). The acetic anhydride derivative showed no significant differences in the peak area ratios for codeine/IS over a period of 24 hours, although the coefficient of variation (CV) was higher for the acetyl derivative than for the TMS derivative of codeine. There was a significant difference associated with the acetyl derivative of morphine at 4 h post derivatization compared to the initial injection (p less than 0.05); however, the acetyl derivative was stable for 24 hours and had a CV of less than 10% at a cutoff of 300 ng/mL.

Acetamides↗
PubMedDate not supplied

Accuracy of five on-site immunoassay drugs-of-abuse testing devices.

Many current "on-site" urine drug-testing products claim performance equivalent to laboratory testing. Five commercially available products (PharmScreen, Roche TestCup, Accusign DOA 2, Status DS, and American Bio Medica-Rapid Drug Screen) were challenged with quality-control specimens of known drug metabolite concentrations, 25% above and 25% below the SAMHSA cutoffs, and with known positive and negative donor specimens previously analyzed by immunoassay and gas chromatography-mass spectrometry. The results indicate discrepancies between claims and performance for all products, particularly with amphetamines. The implications for employer-based drug testing are discussed.

Drug Interactions↗