Biomedical subjects
Publications and source records attributed to Y H Caplan.
The relation between serum osmolality and blood-alcohol was studied prospectively in 565 acute trauma patients. The two measurements were closely correlated. It is therefore possible to estimate the blood-alcohol from serum osmolality to assist in the clinical management of acutely injured patients.
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Studies were performed to evaluate two Abbott TDx ethanol assays, one which is commercially available (TDx-INT) and the other which is under experimental trial (TDx-MTT). Both assays employ radiative energy attenuation (REA) and differ only in the dye used for the chromogen. TDx-INT and TDx-MTT were compared to a headspace gas chromatographic method of analysis. Four types of specimens were studied: serum, urine, postmortem blood, and blood from intoxicated drivers (DWI). Specimens not containing ethanol were also analyzed. Statistical evaluation by least square regression analysis revealed good correlation (greater than 0.98) for each group when ethanol values obtained by either TDx method were compared to the value obtained by gas chromatography. The slopes of the lines ranged from 0.96 to 1.02.
11-Nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) was isolated using solid phase extraction and identified with high performance liquid chromatography (HPLC) with electrochemical detection (EC). HPLC/EC was compared to an established HPLC procedure using ultraviolet (UV) detection. Statistical analysis revealed good precision, linearity, and correlation between the HPLC/EC and HPLC/UV methods. Within-run and between-run precision for the HPLC/EC vs. HPLC/UV analyses yielded coefficients of variation of 4.1 vs. 6.7% and 8.3 vs. 10.9%, respectively. Standard curves over a range of 20 to 160 ng/mL of THC-COOH in fortified urine on four separate analytical runs yielded correlation coefficients of greater than 0.99 for each method. Quantitative results from 15 positive urine specimens also compared favorably between the two methods (r = 0.9923). Using an immunoassay screening technique with confirmation by HPLC/UV and high efficiency thin layer chromatography (HETLC), further evaluation of the HPLC/EC method was achieved by examining 50 cannabinoid positive and 50 cannabinoid negative clinical urine specimens and 500 sequentially collected postmortem urine specimens.
Three methods (IL-182 Co-Oximeter, IL-282 Co-Oximeter, and headspace gas chromatography) for the analysis of carbon monoxide in postmortem blood were studied and compared using a prepared reference standard, Quantra control materials, and 62 postmortem blood specimens. The methods compared favorably with one another. The linear regression equations for the 62 postmortem blood samples (range = 1.0 to 86% saturation) were: IL-282 vs. IL-182, y = 1.11x - 3.10, r = 0.981; IL-182 vs. GC, y = 0.88x + 2.97, r = 0.973; IL-282 vs. GC, y = 1.00x - 1.24, r = 0.986.
Breath specimens (N = 143) from human subjects initially analyzed for ethanol content by infrared spectroscopy were collected onto silica gel. The specimens were retained 1.25 to 2.75 years following adsorption and subsequently analyzed by headspace gas chromatography. The results revealed good overall correlation between the direct and delayed ethanol determinations (r = 0.900). Specimens were collected by police officers following a defined protocol and the results are presented to illustrate practical use and limitations of such a technique.
A case involving an accidental overdose fatality resulting from an intravenous injection of crushed Ritalin (methylphenidate) tablets is presented. The drug was quantified by gas chromatography/nitrogen-phosphorus detection and confirmed by gas chromatography/mass spectrometry. Concentrations of drug were as follows: blood, 2.8 mg/L; bile, 5.7 mg/L; kidney, 3.0 mg/kg; liver, 2.1 mg/kg; and stomach contents, 1.6 mg total. Other drugs and volatile substances were not detected.
A fatal intoxication involving multiple substances including carbamazepine (CBZ), desipramine (DI), and ethylene glycol (EG), in which the blood CBZ concentration was higher than any previously reported in the literature is presented. Each compound, as well as the 10,11-epoxide metabolite of carbamazepine (CBZ-EP), was quantified in blood (CBZ, 79 mg/L; CBZ-EP, 11 mg/L; DI, 4.2 mg/L; EG, 3.6 g/L), bile (CBZ, 69 mg/L; CBZ-EP, 13 mg/L; DI, 23 mg/L; EG, 4.8 g/L), urine (CBZ, 6.5 mg/L; CBZ-EP, 5.7 mg/L; DI, 30 mg/L; EG, 3.3 g/L), stomach contents (CBZ, 280 mg; DI, 49 mg; EG, 2.8 g), liver (CBZ, 75 mg/kg; CBZ-EP, 11 mg/kg; DI, 49 mg/kg; EG, 2.0 g/kg), and kidney (CBZ, 41 mg/kg; CBZ-EP, 11 mg/kg; DI, 23 mg/kg; EG, 1.9 g/kg) using the following analytical techniques: high performance liquid chromatography with ultraviolet detection for CBZ and CBZ-EP, gas-liquid chromatography with mass selective detection for DI and gas-liquid chromatography with flame ionization detection for EG.
A method for the determination of delta-9-tetrahydrocannabinol (THC) in whole blood that employs hexane extraction followed by identification using gas chromatography with nitrogen/phosphorus detection has been developed. The assay is sensitive to 2 ng THC per mL blood and linear to concentrations up to 120 ng/mL (r = 0.998). Precision is demonstrated by coefficients of variation ranging from 3.6 to 9.1% (within run) and 7.1 to 8.0% (between run).
A method for the simultaneous analysis of cocaine (COC), derivatized benzoylecgonine (BE), and derivatized ecgonine methyl ester (EME) has been developed. Blood or urine containing deuterated analogs of the three analytes is extracted by pouring over a Chem-Elut column and eluting with chloroform/isopropanol (9:1). The eluent is collected, split into two equal aliquots, and evaporated to dryness. In one aliquot, dimethylformamide and dimethylformamide dipropyl acetal are allowed to react and to derivatize BE to n-propyl COC. In the other aliquot, 4-fluorobenzoyl chloride, pyridine, and benzene are used to derivatize EME to p-fluoro-COC. COC is not affected by these reactions and may be found in either aliquot. Separation was performed on an HP 5890 GC using an HP-1 capillary column. The oven temperature was initially 100 degrees C for 1 minute, then programmed at 30 degrees/minute to a final temperature of 260 degrees C. The GC/MS was operated in the SIM mode, and the masses monitored were 303, 321, and 331 respectively for COC and derivatized EME and BE, and 308, 324, and 334 for the respective deuterated internal standards. The assay showed a minimum linear range of 0.05-2.0 mg/L for COC and 0.10-4.0 mg/L for each of the metabolites.
The TDx fluorescence polarization immunoassays (FPIA) for some therapeutically monitored drugs (lidocaine, phenytoin, phenobarbital) were applied to the analysis of postmortem blood specimens. After an initial calibration using the appropriate TDx calibrators, blood bank blood fortified with known amounts of drug was analyzed by FPIA. Postmortem blood specimens containing the drugs, postmortem specimens not containing the drugs of interest (negatives), and randomly selected postmortem blood specimens fortified with known amounts of the drugs were analyzed by the FPIA and reference gas chromatographic (GC) methods. Concentrations determined in blood bank and postmortem blood specimens showed excellent correlation between the two methods and produced lines with slopes ranging from 0.98 to 1.08. In each case the correlation coefficient was greater than 0.97. Analysis of all negative specimens produced FPIA values below the limit of quantitation of the reference GC assay.
The stability of cocaine (COC) in blood bank blood, postmortem human whole blood, and buffers was evaluated with consideration for the presence of the degradation products, benzoylecgonine (BE) and ecgonine methyl ester (EME). At COC concentrations commonly seen, the rate of COC hydrolysis was independent of concentration. COC was stable in blood for at least 150 days if the blood was adjusted to pH 5 and preserved with 2% NaF or organophosphates and maintained at 4 degrees C or lower. Without preservation, most COC hydrolyzed to EME. The addition of a pseudocholinesterase (PChE) inhibitor without a reduction of pH caused COC to hydrolyze to BE. COC also hydrolyzed to BE in phosphate buffer. The rate of COC hydrolysis in all studies increased with increasing pH and temperature. COC was more stable in unpreserved postmortem blood than blood bank blood due to the lower pH of the former. The incubation of COC in enzyme solutions provided further evidence of the generally accepted hypothesis that COC is hydrolyzed to EME by PChE and to BE by chemical hydrolysis. In unpreserved blood, BE was more stable than EME at room temperature. There was little loss of BE or EME at refrigerated temperature over a period of 35 days and no evidence that EME or BE could be hydrolyzed enzymatically.
This study evaluated the capability of the Abbott ADx assays to test for phencyclidine (PCP) and barbiturates in urine specimens by comparison to TDx, EMIT, and gas chromatographic/mass spectrometric (GC/MS) methods. Within-run and between-run precision were determined using three control samples (35, 100, and 250 ng/mL PCP; 0.4, 0.6, and 1.0 mg/L secobarbital) tested over a two-week period. Controls were analyzed in both single assay (batch) and multiple assay (combination) modes. Within-run coefficients of variation (CVs) for the three PCP controls were 2.4, 2.6, and 2.2%, respectively; the between-run CVs were 4.0, 3.5, and 2.8%, respectively. The within-run CVs for the three barbiturate controls were 3.0, 2.7, and 2.7%, respectively; the between-run CVs were 5.6, 4.7, and 4.5%, respectively. Fifty specimens not containing PCP or barbiturates, 50 specimens containing PCP, and 50 specimens containing barbiturates were tested by ADx, TDx, EMIT, and GC/MS. The methods compared favorably and no false positive or false negative results were obtained by any immunoassay method for any assay when compared to GC/MS.
The Coat-A-Count solid phase 125I Fentanyl Radioimmunoassay was evaluated with respect to linearity and precision using equine urine fortified with fentanyl and then compared with a gas chromatographic/mass spectrometric method for quantification of fentanyl in urine. The RIA assay was found to be linear over the urine fentanyl concentration range of 0.25 to 7.5 ng/mL and precise with coefficients of variation (CV) ranging from 9.6 to 19.3%. The RIA calibrators, ranging in fentanyl concentrations from 0.25 to 7.5 ng/mL, and controls, at mean fentanyl concentrations of 0.46 and 1.32 ng/mL, were compared by both the RIA and GC/MS methods. The cross-reactivity with the 125I RIA test was determined for the fentanyl metabolites, norfentanyl and hydroxyfentanyl, and found to be 5% and 35%, respectively. The illicit fentanyl analogs were found to show significant cross-reactivity, ranging from 20 to 100%. The 125I RIA was compared to GC/MS quantifications of fentanyl in 35 positive and 20 negative case urine specimens.
Many studies have been published comparing blood (B) ethanol (EtOH) and vitreous humor (VH) EtOH concentrations. We conducted a similar study of routinely collected specimens to determine (1) whether the reported average VH/B ratios are consistent, (2) the percentage of cases with VH/B ratios outside of the expected range, and (3) the magnitude of B EtOH that can be associated with negative VH EtOH (less than 0.01 g/dL). VH EtOH less than 0.01 g/dL was associated with 41 specimens; 34 specimens had B EtOH less than 0.03 g/dL while a B EtOH as high as 0.12 g/dL was measured. For B EtOH less than 0.10 g/dL, 67% had VH EtOH within 0.02 g/dL of B EtOH (N = 101). For B EtOH greater than or equal to 0.10 g/dL, the VH/B EtOH ratio ranged from 0.10 to 1.91; the mean ratio was 1.17 and the median ratio was 1.18 (N = 205); and 64% had a ratio between 1.00 and 1.39. Vitreous humor can be used to facilitate understanding the significance of postmortem blood EtOH concentrations.
A fatal case attributed to flecainide intoxication is presented. Quantitation was by capillary gas chromatography with nitrogen-phosphorus detection. The flecainide concentration in the blood was 13 mg/L as compared to a therapeutic range in serum of 0.2-1.0 mg/L. Flecainide concentrations in other specimens were as follows: bile, 160 mg/L; urine, 54 mg/L; vitreous humor, 7.4 mg/L; liver, 180 mg/kg; kidney, 74 mg/kg; and stomach contents, 120 mg.
Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.