Biomedical subjects

E T Shimomura

Publications and source records attributed to E T Shimomura.

6 recordsLinked to original sources

PubMed2001

Urinary excretion profiles for total morphine, free morphine, and 6-acetylmorphine following smoked and intravenous heroin.

Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2 (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3-22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/mL for low and high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150-2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6.1-568 (124) ng/mL. In general, the first urine void had the peak 6-AM concentration and was the only specimen positive at a 10-ng/mL cutoff. As previously reported urine concentrations varied greatly between subjects and within subjects with time after dosing but were much more predictable when values were reported as amount of drug per unit of creatinine. The range (median) values for percent of heroin excreted into urine as Tmor was 12.8-88.5% (51.0).

Administration, Inhalation↗

PubMed2001

Examination of postmortem fluids and tissues for the presence of methylecgonidine, ecgonidine, cocaine, and benzoylecgonine using solid-phase extraction and gas chromatography-mass spectrometry.

BACKGROUND: During the smoking of crack cocaine (COC), methyl ecgonidine (MED) is formed as one of the pyrolysis products. Once in the body, MED is converted to ecgonidine (ED) through several processes that include spontaneous hydrolysis and enzymatic hydrolysis. The presence of MED and/or ED could provide valuable information to help determine antemortem conditions in cases where COC is involved. Our goal was to examine postmortem tissues and fluids for the presence of MED, ED, COC, and benzoylecgonine (BZ). METHODS: Liver, brain, blood, and urine specimens obtained from 15 postmortem cases were extracted using solid-phase extraction, derivatized, and analyzed using gas chromatography-mass spectrometry with selective-ion monitoring. RESULTS: Median concentrations (range) of drugs observed in postmortem liver, brain, blood, and urine were 0 (0-10) ng/g, 7 (0-92) ng/g, 0 (0-42) microg/L, and 62 (0-2030) microg/L, respectively, for MED; 655 (90-3274) ng/g, 22 (0-52) ng/g, 119 (13-773) microg/L, and 456 (109-7452) microg/L, respectively, for ED; 57 (0-503) ng/g, 187 (0-1403) ng/g, 12 (0-88) microg/L, and 1208 (37-28 062) microg/L, respectively, for COC; and 821 (45-4980) ng/g, 524 (46-5153) ng/g, 458 (30-2071) microg/L, and 6768 (917-116 430) microg/L, respectively, for BZ. MED was detected in 12 of 15 postmortem cases. The concentrations were highest in urine compared with liver, brain, and blood. The hydrolysis product ED was detected in all postmortem cases, and the concentrations were substantially higher than MED in all liver, blood, and urine specimens. CONCLUSION: ED may be a more useful indicator of crack COC smoking.

Body Fluids↗

PubMed2000

Detection times and analytical performance of commercial urine opiate immunoassays following heroin administration.

The Federal Workplace Drug Testing Program changed urine screening and confirmation cutoff concentrations for opiate testing from 300 to 2000 ng/mL in 1998. Morphine was the designated target compound. An additional heroin metabolite, 6-acetylmorphine (6-AM), was added to the testing procedure with a cutoff concentration > or = 10 ng/mL. Testing of 6-AM was required if morphine was positive to assist in medical review. A comparison of the new opiate cutoff concentrations was made with the older cutoff concentration at 300 ng/mL. Six commercial opiate immunoassays, four with a 300-ng/mL cutoff, ONLINE, EMIT, CEDIA and AxSym, and two with 2000-ng/mL cutoffs, ONLINE and EMIT, were selected to test 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCl and four smoked 3.5-, 5.2-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control specimens were added to the study set to assess linearity, cross-reactivity, and interference. Total morphine, free morphine, and 6-AM were measured in each sample by gas chromatography-mass spectrometry (GC-MS). Linearity, cross-reactivity, and interference results for each immunoassay are described. Detection times, sensitivity, specificity, and efficiency of each assay were determined using data from the specimens collected after heroin administration. Detection times for morphine using the 300-ng/mL cutoff assays was approximately 12 h for low dose and 24 to 48 h for higher doses of heroin. For the two 2000-ng/mL cutoff concentration assays detection time was about 12 h. This was also the detection time for 6-AM by GC-MS. ONLINE had the lowest sensitivity, 60-74%, highest specificity, 98.8-100%, and least interference from a selection of common over-the-counter drugs and opioids. Increasing the cutoff to 2000 ng/mL from 300 ng/mL increased efficiencies of the assays from 72.7 to 82.6% to over 97%.

Administration, Inhalation↗

PubMed1999

A practical approach to determine cutoff concentrations for opiate testing with simultaneous detection of codeine, morphine, and 6-acetylmorphine in urine.

BACKGROUND: Both the Department of Defense (DoD) and the Department of Health and Human Services (DHHS) currently require two confirmation tests to verify use of heroin, one test for total morphine and a separate test for 6-acetylmorphine (6-AM). Our aim was to determine appropriate free-codeine, free-morphine, and 6-AM cutoff concentrations that could be substituted for total-morphine, total-codeine, and 6-AM cutoff concentrations and to develop a less labor-intensive method for measuring codeine, morphine, and 6-AM. METHODS: Urine samples containing opiates were extracted, derivatized, and analyzed using gas chromatography-mass spectrometry with selective ion monitoring. RESULTS: The limits of detection for codeine, morphine, and 6-AM were 6, 5, and 0.5 microg/L, respectively. Recoveries were >90%. Quantification was linear over the concentration range of 6-1000 microg/L for codeine, 5-5000 microg/L for morphine, and 0.5-800 microg/L for 6-AM. Cutoff concentrations for confirmation of opiates were 100, 100, and 10 microg/L for free codeine, free morphine, and 6-AM. CONCLUSION: The proposed cutoff concentrations for free morphine and 6-AM provide better detection windows for morphine and heroin use than the cutoff concentrations for total morphine and 6-AM used at present. Detection of free codeine, instead of total codeine, simplifies interpretation of codeine use. The single-extraction method enables simultaneous, less labor-intensive analysis of morphine, codeine, and 6-AM.

Codeine↗

PubMed1993

Military drug positive rates in the European Theater drug rates in Europe.

Urine samples were collected from Air Force and Army service members within the European Theater and analyzed for drugs of abuse employing radioimmunoassay and gas chromatography/mass spectroscopy (GC/MS). Data collected from January 1985 through December 1991 indicate that the total positive rate decreased from 4.67% to 0.69%. Of the drugs tested, tetrahydrocannabinol (THC) was the drug abused most in the European Theater during this time period.

Humans↗

PubMed1990

Quality assurance in drug testing laboratories.

Drug testing is currently regulated for Department of Defense and other federal agency programs and many of the QA actions listed in this article are mandated in the regulations cited. This trend will probably continue in an effort to ensure high-quality test results and may expand into private sector testing. Also, more drugs may be added to the list of the five currently mandated for federal agencies. It remains to be seen if the certified DTLs avoid the pitfalls of past programs. A good QA program will undoubtedly be the key to success.

Government Agencies↗