Biomedical subjects

B D Paul

Publications and source records attributed to B D Paul.

44 records · Page 3Linked to original sources

PubMedDate not supplied

Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration.

The urinary excretion profile of free and conjugated codeine and morphine was determined by GC/MS for four healthy male subjects after intramuscular administration of 60- and 120-mg doses of codeine. Codeine and metabolites were rapidly excreted with the majority of drug appearing in the first 24 h. No dose-related differences in metabolism were observed. The initial ratio of total codeine to total morphine was substantially greater than 1.0 but declined over time. For two of the four subjects, the codeine-morphine ratio declined below 1.0 late in the elimination phase. With a 300-ng/mL cutoff, one subject tested positive on more than one occasion for total morphine and negative for codeine during the terminal elimination phase. The data indicate that urine codeine-morphine ratios are not reliable indices of the type of opiate exposure.

Codeine↗

PubMedDate not supplied

Forensic drug testing for opiates. IV. Analytical sensitivity, specificity, and accuracy of commercial urine opiate immunoassays.

Four commercial immunoassays, TDx Opiates (TDx), Coat-A-Count Morphine in Urine (CAC), Abuscreen Radioimmunoassay for Morphine (ABUS) and Emit d.a.u. Opiate Assay (EMIT), were tested for sensitivity, specificity, and accuracy with urine specimens containing known amounts of opiates and opiate metabolites. The immunoassays were evaluated in a semiquantitative mode by comparison of morphine equivalents to GC/MS assay of free and total morphine and codeine or to target concentrations. In all cases, the apparent sensitivities of the assays were higher than those required for detection of morphine at cutoffs mandated by the Health and Human Services guidelines for testing of Federal workers. The apparent specificities of the immunoassays varied considerably. The CAC assay was found to be highly selective for free morphine, whereas TDx, ABUS, and EMIT demonstrated broad cross-reactivity with other opiates. Comparison of semiquantitative results from the immunoassays with GC/MS data indicated a high degree of accuracy for determination of morphine levels. Generally, the patterns of sensitivity and cross-reactivity were unique for each assay, indicating that a detailed knowledge of assay performance characteristics is necessary for accurate interpretation of forensic urine testing data.

Forensic Medicine↗

PubMedDate not supplied

Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays.

Urine specimens collected after heroin, morphine, and codeine administration were tested by four commercial opiate immunoassays (TDx, CAC, ABUS, and EMIT) and GC/MS. Quantitative immunoassay results (morphine equivalents) were compared with results by GC/MS for total morphine, free morphine, or total codeine. Mean detection times for the broadly cross-reacting immunoassays (TDx, ABUS, and EMIT, 300 ng/mL cutoff) ranged from 15-44 hours following heroin and morphine administration and 33-54 hours following codeine administration. Detection times obtained with CAC (25 ng/mL cutoff) tended to be somewhat shorter as a result of the high selectivity of the antibody for free morphine. High correlations over a wide concentration range were obtained for TDx, CAC, and ABUS versus GC/MS, with specimens collected after heroin and morphine administration. EMIT showed a high correlation over a narrow concentration range (0-1000 ng/mL) with heroin and morphine specimens, but responses plateaued at higher concentrations. There was substantial variability in immunoassay responses with specimens collected after codeine administration. Generally, this study demonstrated that immunoassay responses for opiate urine testing can be used as a semi-quantitative guide for GC/MS confirmation; however, the presence of codeine increased variability and diminished the accuracy of the immunoassay response.

Codeine↗

PubMedDate not supplied

Effects of pyridinium chlorochromate adulterant (urine luck) on testing for drugs of abuse and a method for quantitative detection of chromium (VI) in urine.

Pyridinium chlorochromate (PCC) as an adulterant is popular for concealing drug-positive results. When 11-nor-delta9-THC-9-carboxylic acid (THC-acid) in urine was treated with 2 mmol/L of PCC (Cr6+ 104 microg/mL), 58-100% of the THC-acid was lost. The loss increased with decreasing pH and increasing reaction time (0-3 days). Free codeine and free morphine remained unaffected by PCC at pH within the physiological range of the urine (pH 5-7). At lower pH, the loss of free morphine varied from 0 to 100%. Amphetamine, methamphetamine, benzoylecgonine, and PCP remained unaffected by PCC when exposed to the oxidant for three days in urine pH of 3-7. Chromium (VI) from PCC in a urine solution was detected by a color reaction with 1,5-diphenylcarbazide (DPC). When the reagent was added to the urine, an immediate red-violet color appeared. The chromium-DPC complex showed a characteristic absorption peak at wavelength 544 nm with a shoulder at wavelength 575 nm. The ratio of absorption was used to identify the chromium compound. The concentration of chromium (VI) was determined by measuring absorption at wavelength 544 nm and was linear over 0.5-20 microg/mL. The limit of detection of the procedure was 0.37 microg/mL.

Anti-Infective Agents↗

PubMedDate not supplied

Simultaneous identification and quantitation of codeine and morphine in urine by capillary gas chromatography and mass spectroscopy.

An analytical procedure for simultaneous determination of codeine and morphine in urine is described. The detection of codeine and morphine is based on liquid-liquid extraction and derivatization to the acetylated compounds. The acetylated codeine and morphine are separated by capillary gas chromatography and identified mass spectrometrically by selected ion monitoring (SIM). Quantitative determination was carried out by SIM using nalorphine as internal standard. Excellent linearity was obtained over a concentration range of 25 to 800 ng/mL. The overall recovery for codeine and morphine in the extraction was found to be 58% and 40%, respectively. The on-column sensitivity for both compounds was 2 ng at a peak-to-noise ratio of 5:1. The derivatives, acetylcodeine, diacetylmorphine, and diacetylnalorphine were stable at room temperature for 72 hr.

Codeine↗

PubMedDate not supplied

New agents for prostatic cancer activated specifically by prostatic acid phosphatase.

Potential cytotoxic compounds (spindle poisons) are being designed for the treatment of prostatic carcinoma, using the structural requirements of the substrates for prostatic acid phosphatase (PAP). Colchicine has been modified in ring C to give colchiceinamides of substituted ethanolamines and ethanolaminephosphates. Another new series of compounds modifying ring B of thiocolchicine have been prepared. Three O-phosphates of the thiocolchicine series have also been made. One has been examined for its specificity toward PAP. Some toxicity data of these compounds in mice have also been reported. Colchiceinamide-(L)-ephedrinephosphate has been examined in stumptail monkeys and some preliminary results are reported here.

Acid Phosphatase↗

PubMedDate not supplied

Design of spindle poisons activated specifically by prostatic acid phosphatase (PAP) and new methods for PAP cytochemistry.

By taking advantage of the structural requirements of the substrates for prostatic acid phosphatase (PAP), which consist of steric hindrance and the presence of basic nitrogen in the molecule, potential cytotoxic agents (spindle poisons) are being designed that will become enzyme activated specifically by PAP. Colchicine has been converted to colchiceinamides of substituted ethanolamines and o-phosphoethanolamines. The rate of hydrolysis of the latter by human prostatic tissue as compared to the rate of hydrolysis by human kidneys (P/K ratio) is given and indicates a significant degree of specificity for PAP. Some preliminary toxicity data in mice are also given. New thiocolchicine derivatives with phosphates on ring B are also being prepared for study and some preliminary toxicity data are given. The observation in biochemical experiments that phosphorylcholine is a very specific substrate for PAP has led us to develop specific cytochemical methods for PAP for both light and electron microscopy. Preliminary observations are given and good evidence is provided that PAP is not a lysosomal enzyme, unlike other acid phosphatases. Furthermore, PAP is to other acid phosphatases what the cholinesterases are to other esterases. Since the acid phosphatase that is able to hydrolyze phosphorylcholine is characteristic of prostatic epithelium, this is the acid phosphatase that is referred to be the designation of PAP. Other acid phosphatases (both lysosomal and nonlysosomal) in prostatic epithelial cells are not demonstrated by this substrate and hence are not included in this designation.

Acid Phosphatase↗

PubMedDate not supplied

Design of a novel regulatory circuit for expression of restriction endonucleases.

We have developed a new strategy with a very tight control for the expression of cloned genes. The system employed here is the T7 promoter-based expression system in which transcription activator protein C of bacteriophage Mu (Mu C) has been cloned to serve as a repressor in the regulatory circuit. The system also includes pLysE, which encodes T7 lysozyme, an inhibitor of T7 RNA polymerase. This ensures tight regulation of cloned genes in the uninduced state. Upon induction, the expressed Mu C protein binds to its cognate site thereby repressing lys transcription driven by the tet promoter. In order to evaluate the tight control achieved in the system, and to check leaky expression, if any, we have cloned the gene for the SmaI restriction endonuclease without its cognate methylase. For this purpose, a dicistronic unit was constructed by cloning the smaIR gene downstream of the Mu C gene. SmaI expression was observed only in the induced cell extracts, demonstrating a tight control. The system could be used to express the genes of other cloned restriction enzymes and has the potential for general applications.

Bacteriophage T7↗