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Biomedical subjects

S J Mulé

Publications and source records attributed to S J Mulé.

At least 19 recordsLinked to original sources

Rendering the "poppy-seed defense" defenseless: identification of 6-monoacetylmorphine in urine by gas chromatography/mass spectroscopy.

We report a sensitive, rapid, quantitative gas chromatographic/mass spectroscopic method for measuring the 6-monoacetylmorphine (6-MAM) metabolite of heroin in 0.5 mL of human urine. After a simple liquid-liquid extraction and derivatization, the trimethylsilyl derivative of 6-MAM is identified from its retention time (total ion current) and by selected ion monitoring. The limit of detection was 10 micrograms/L, corresponding to 0.2 ng of trimethylsilyl-6-MAM injected into the gas chromatograph/mass spectrometer. The presence of 6-MAM in urine is indicative of heroin. 6-MAM is not present in poppy seeds or in urine after the ingestion of products containing poppy seed.

False Positive Reactions↗

Quantitation of l-alpha-acetylmethadol and its metabolites in human serum by capillary gas-liquid chromatography and nitrogen detection.

A procedure is described for the simultaneous measurement of l-alpha-acetylmethadol and its two pharmacologically active metabolites: noracetylmethadol and dinoracetylmethadol. In the method an intramolecular conversion reaction of the two metabolites to their amide configuration is utilized. The reaction is performed while the metabolites are still in the serum. Following solvent extraction the samples are analyzed by capillary gas-liquid chromatography coupled with nitrogen detection. Quantitation is achieved by internal standardization. The lower limit of sensitivity is 5 ng/ml in serum. Absolute sensitivity is 0.1 ng for all three compounds. The advantages over other procedures are: speed due to the single extraction step; increased recovery of noracetylmethadol and dinoracetylmethadol due to decreased polarity of the amides; greater stability of the metabolites in the amide configuration; better chromatographic quantitation and separation because detector response for the amides is greater than it is for the original configuration of the metabolites and the area of the chromatographic tracing is free of interfering substances.

Chromatography, Gas↗

Simultaneous determination of nicotine and cotinine in human plasma by nitrogen detection gas-liquid chromatography.

Human plasma levels of nicotine and its principal metabolite, cotinine, were simultaneously quantitated by gas-liquid chromatography combined with nitrogen selective detection. Nicotine, cotinine, and the added internal standard ketamine are extracted from plasma at basic pH into methylene chloride, back-extracted into acid, and then re-extracted into methylene chloride. Analysis is carried out on a packed glass column of 3% SE-30 while column temperature is programmed from 150 to 200 degrees C. Detector response is linea over the range of 2 to 50 ng/mL nicotine and 50 to 500 ng/mL cotinine. The method was validated on 150 plasma samples obtained from habitual smokers. Mean levels of 19.5 and 219 ng/mL were found for nicotine and cotinine, respectively. Both the mean and the range of the levels were in agreement with previously reported plasma levels for nicotine and cotinine.

Chromatography, Gas↗

Comparative effects of cocaine and pseudococaine on EEG activities, cardiorespiratory functions, and self-administration behavior in the rhesus monkey.

The effects of cocaine and pseudococaine on the EEGs, heart and respiratory rates, and self-administration behavior were studied in rhesus monkeys. An intravenous injection of cocaine (2.5 and 4.0 mg/kg) in the monkey produced low-voltage fast waves (LVFWs) in the EEGs and behavioral hyperexcitation accompanied by marked increases in the heart and respiratory rates with mydriasis and excessive salivation. In contrast, pseudococaine produced high-voltage slow waves (HVSWs) in the EEGs and behavioral depression accompanied by the same symptoms of the autonomic functions as those produced by cocaine. Both isomers were self-administered by the monkeys. During cocaine self-administration sessions, the animals showed hyperexcitation in their overall behavior, while with pseudococaine they showed almost normal behavioral responses. These results suggest that cocaine produced excitatory effects and pseudococaine inhibitory effects on the EEGs and behavior. Both isomers stimulate the heart and respiratory rates, and were self-administered by the monkeys.

Animals↗

Radioimmunoassay of methaqualone in human urine compared with chromatographic methods.

The 125I-radioimmunoassay for methaqualone in human urine was evaluated by a comparison with newly modified gas-liquid chromatographic and thin-layer chromatographic methods. The statistically significant sensitivity value for the radioimmunoassay was at 2 microgram of methaqualone per liter of urine. The coefficient of variation was 2.88 +/- 0.39% interassay and 2.71 +/- 0.16% intraassay. There was cross-reactivity only with metabolites of methaqualone, 4'-hydroxymethaqualone being twice as sensitively measured as methaqualone. There was complete agreement between results by radioimmunoassay and by gas-liquid chromatography in 96.7% of the samples analyzed. Only 1.2% of the radioimmunoassay values were false positives, and 2.1% false negatives (phi = 0.8917, P less than 0.001). Comparisons between the thin-layer chromatographic data and the gas-liquid chromatographic or radioimmunoassay data showed less agreement because of the 50- to 200-fold higher sensitivity of the latter two techniques. Gas-liquid chromatography therefore appears to represent the best reference method for the evaluation of the radioimmunoassay, which appears to be a very sensitive and reliable technique for detecting methaqualone and its metabolites in human urine.

Chromatography, Gas↗

Evaluation of the radioimmunoassay for benzoylecgonine (a cocaine metabolite) in human urine.

The 125I-radioimmunoassay (RIA) for benzylecgonine (cocaine metabolite) in urine was evaluated by comparison with gas-liquid chromatography (GLC) and thin-layer chromatography (TLC) and the Enzyme-Multiplied Immunoassay Technique (EMIT). By RIA, a statistically significant concentration, 2 microng/liter, was observed for urinary benzoylecgonine. The coefficient of variation for the RIA was 2.58+/-0.38% inter-assay and 2.20+/-0.14% intraassay. There was cross-reactivity with cocaine (more reactive than benzoylecgonine) and other members of the tropane family of alkaloids. There was agreement between results by RIA and GLC in 95.5% of the samples, between RIA and TLC in 87.0%, and between RIA and EMIT in 84.5%. The percentage of true false-positives was 3.5% for the RIA in comparison to GLC, 8.8% in comparison to TLC, and 9.1% in comparison to EMIT. True false-negatives were insignificant (0 to 1.0%). GLC and RIA results correlated highly (phi=0.908). GLC, therefore, was the best comparison method for this evaluation study. RIA for benzoylecgonine is sensitive, reproducible, and reliable for the detection of cocaine in urine.

Chromatography, Gas↗

Quantitative determination of naltrexone and beta-naltrexol in human plasma using electron detection.

A gas-liquid chromatographic method is described for the determination of naltrexone and beta-naltrexol in human plasma following derivatization with pentafluoropropionic anhydride using electron capture detection. The lower sensitivity of the method for absolute standards is 5-10 pg. Following an acute 100-mg dose to a subject, peak levels of naltrexone of 15 ng/ml at 2 h and of beta-naltrexol 84 ng/ml at 4 h were observed. The levels of both compounds decreased by 24 h after the dose: naltrexone to 2.9 ng/ml and beta-naltrexol to 25 ng/ml. Following chronic administration for two weeks of 100 mg per day the peak levels of naltrexone and betanaltrexol increased to 26.9 and 131 ng/ml at 2 h, respectively, but by 24 h both compounds were at levels similar to those following a single dose. Thus no accumulation of either drug ro metabolite in the plasma was seen following chronic naltrexone administration.

Chromatography, Gas↗