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Biomedical subjects

L E Edinboro

Publications and source records attributed to L E Edinboro.

16 recordsLinked to original sources
PubMed2006

The effect of alkylamine additives on the sensitivity of detection for paclitaxel and docetaxel and analysis in plasma of paclitaxel by liquid chromatography-tandem mass spectrometry.

The formation of multiple molecular ions, especially due to sodium adduct ion formation, is commonly observed in electrospray mass spectrometry and may make reproducible and sensitive quantitation difficult. The objective of this work was to investigate the underlying mechanism involved in the suppression of multiple molecular ion formation and to improve the sensitivity of detection for the two anti-neoplastic agents paclitaxel and docetaxel. The results showed that alkylamine additives could significantly improve the detection of paclitaxel and docetaxel by suppression of multiple molecular ions through preferential formation of a predominant alkylamine adduct ion. Possible binding sites, binding interactions and binding competition were investigated for the sodium adduct and alkylamine adduct ions using various experimental techniques. The formation of a predominant amine adduct ion may be due to increased surface activity in the droplet. The optimal alkylamine for both analytes was octylamine, which increased peak heights of paclitaxel and docetaxel 4.8 and 3.7-fold (n = 3), respectively. The precision of the signals for the analytes was also improved 5.7-fold. A quantitative assay in plasma for paclitaxel was partially validated for the calibration range 1.0-1000 ng/mL (r = 0.9977) when using 0.05% octylamine as a reconstitution solution additive. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.5 and 0.9 ng/mL, respectively. Acceptable precision, accuracy, specificity and sample stability were demonstrated for this assay. This approach may prove useful for other analytes with similar binding sites.

Amines↗
PubMed1997

Evaluation of a colloidal metal immunoassay device for the detection of tricyclic antidepressants in urine.

BACKGROUND: The sensitivity and selectivity of a colloidal metal immunoassay device (Triage Plus TCA) which is designed for the rapid detection of tricyclic antidepressant drugs in urine at a total tricyclic antidepressant concentration of 1000 ng/mL or greater were evaluated. METHODS: The sensitivity of the Triage Plus assay was determined by adding known amounts of amitriptyline, nortriptyline, imipramine, desipramine, doxepin and desmethyl-doxepin to drug free urine. The selectivity of the assay was determined by adding known concentrations of 32 drugs or drug metabolites commonly encountered in emergency department admissions to drug free urine. Triage Plus results from clinical urine specimens containing either amitriptyline, nortriptyline, imipramine, desipramine, doxepin and desmethyl-doxepin were compared to those obtained with thin layer chromatography and high performance liquid chromatography. RESULTS: Triage Plus yielded a positive response to gravimetrically prepared urines of tricyclic antidepressant at the stated cut-off value (1,000 ng/mL), and at 80% (800 ng/mL) and 50% (500 ng/mL) of the cut-off with amitriptyline, nortriptyline, imipramine, desipramine and doxepin. Other tricyclic antidepressant drugs, clomipramine and protriptyline were positive at 1000 ng/mL. Significant cross-reactivity was observed only with cyclobenzaprine at 1000 ng/mL. No significant cross reactivity was found at 1.0 g/L for 32 drugs commonly encountered in emergency department admissions. A 95% (70/74) agreement of positive tricyclic antidepressant results was observed between Triage Plus and thin layer chromatography. Discordant urines were found by high performance liquid chromatography to contain tricyclic antidepressant concentrations below the cut-off value of the colloidal metal assay. CONCLUSION: Triage Plus was found to be an accurate device for the detection of tricyclic antidepressants in urine at the stated cut-off value of 1000 ng/mL tricyclic antidepressant. With the exception of cyclobenzaprine, significant cross-reactivity was not observed with other drugs commonly encountered in emergency department admissions.

Antidepressive Agents, Tricyclic↗
PubMed1997

Fatal fentanyl intoxication following excessive transdermal application.

The case history and toxicological findings of a fatal fentanyl intoxication due to the application of multiple transdermal patches are presented. An 83 year-old white female with terminal cancer was found dead with three 100 mg/h fentanyl patches on her chest. The autopsy and subsequent histological studies revealed extensive areas of gastric carcinoma, a large atrial tumor, ulceration of esophagus, metastasis of peripancreatic lymph nodes and a recent surgical removal of part of the lower lobe of the left lung. Toxicological analysis by GC/MS yielded fentanyl concentrations of blood, 25 ng/mL; brain, 54 ng/g; heart 94 ng/g; kidney 69 ng/g; and liver 104 ng/g. The cause of death was determined to be fentanyl overdose and the manner of death was ruled undetermined as the investigation was unable to conclusively establish whether this was an accidental overdose, a suicide, an assisted suicide, or possible a homicide. This case demonstrates the need for caution in self-administration of transdermal fentanyl patches, in particular, the dangers inherent in the application of multiple patches which can result in the release of potentially toxic or lethal doses.

Administration, Cutaneous↗
PubMed1995

Fatal morphine poisoning in a child due to accidental oral ingestion.

A case of fatal intoxication of an 8 year old child due to accidental oral ingestion of morphine is presented. Following a tonsillectomy and release from the hospital the decedent was prescribed meperidine syrup 50 mg per teaspoon (tsp) to be taken 2 tsps every 4 h. A pharmacist when filling her prescription mistakenly dispensed Roxanol which contained 20 mg/ml morphine sulfate. She took 1 or 2 tsp of the prescription prior to bed and was found dead the next morning. Autopsy findings were unremarkable. Quantitation by gas chromatography/mass spectrometry (GC/MS) yielded the following morphine results: blood, 0.128 mg/l; bile, 135 mg/l and stomach contents, 16 mg/l (2.3 mg total). Based upon the clinical history, autopsy and toxicology finding the cause of death was determined to be poisoning by morphine and the manner of death accidental.

Administration, Oral↗
PubMed1994

Detection of benzodiazepines and tribenzazolams by TRIAGE: confirmation by solid-phase extraction utilizing SPEC.3ML.MP3 microcolumns and GC-MS.

A new point-of-care urine drugs-of-abuse testing device, the BIOSITE TRIAGE, was evaluated for detection of benzodiazepines (BNZs). TRIAGE utilizes a unique, competitive, visual immunoassay methodology to simultaneously detect seven classes of drugs of abuse. Because of the unique ASCEND Multimmunoassay technology, conflicting results may arise when TRIAGE is compared with conventional immunoassay techniques. Apparent TRIAGE BNZ false-positive results may occur when gas chromatographic-mass spectrometric (GC-MS) confirmation utilizes oxazepam as the analyte used to confirm the presence of BNZs. TRIAGE BNZ results were correlated with those of Syva EMIT, (n = 106, overall agreement 85%). Both negative and positive urine samples were tested by GC-MS for the following drugs: oxazepam, nordiazepam, desalkylflurazepam, OH-ethylflurazepam, lorazepam, temazepam, alpha-OH-alprazolam and alpha-OH-triazolam. Urine samples were extracted using the new ANSYS SPEC.3ML.MP3 solid-phase extraction microcolumn. The ANSYS procedure for BNZs was modified to include desalkylflurazepam, OH-ethylflurazepam, lorazepam, temazepam, alpha-OH-alprazolam, and alpha-OH-triazolam. Deuterated oxazepam and alpha-OH-alprazolam were used as internal standards. Limits of quantitation (LOQs) ranged from 25 to 100 ng/mL with a limit of detection of 25 ng/mL for all analytes. Individual analytes demonstrated within-run precision and between-run precision ranging from 0.9 to 4.7% CV and 1.3 to 16.9% CV, respectively. All analytes were linear from their LOQs to 1000 ng/mL.

Benzodiazepines↗
PubMed1994

Disposition of cocaine and norcocaine in blood and tissues of B6C3F1 mice.

The biodisposition of cocaine and norcocaine in blood and tissues of immunological importance in B6C3F1 mice following exposure to cocaine or cocaine plus an organophosphate esterase inhibitor, diazinon, is presented. Analysis of specimens was by gas chromatography-mass spectrometry. Results from these studies indicate that pretreatment with diazinon significantly increases cocaine and norcocaine concentrations in the blood, spleen, thymus, and liver. Following acute exposure to cocaine-diazinon, cocaine was found in the spleen and thymus up to 1 hour after exposure. Norcocaine was not detected at this time. Following 7-day exposure to cocaine-diazinon, both cocaine and norcocaine were found in liver, blood, and spleen up to 1 hour after the last exposure; however, only cocaine was detected in the thymus at 1 hour. Cocaine and norcocaine were not detected in any tissues 24 hours after the last exposure.

Animals↗
PubMed1994

Hepatic lidocaine metabolism and liver histology in patients with chronic hepatitis and cirrhosis.

Recent advances in the medical and surgical treatment of chronic hepatitis and cirrhosis have made it increasingly important to develop noninvasive tests of liver function. Our study has evaluated the hepatic conversion of lidocaine to its primary metabolite monoethylglycinexylodide and compared this with liver histological findings in 225 patients with chronic hepatitis (161 with hepatitis C, 23 with hepatitis B, 21 with autoimmune hepatitis and 20 with cryptogenic hepatitis). One hundred seven (47.7%) patients had cirrhosis at the time of evaluation. A decline in monoethylglycinexylodide production was observed with worsening liver histological conditions from a mean of 81.5 +/- 7.0 ng/ml in patients with chronic persistent hepatitis to 61.2 +/- 5.5 ng/ml for chronic active hepatitis and 20.9 +/- 1.5 ng/ml in patients with cirrhosis (p < 0.05). A further stepwise decline in monoethylglycine xylodide production was observed with worsening Child class: from 25.5 +/- 2.2 ng/ml for class A patients to 8.9 +/- 1.4 ng/ml for patients with Child class C disease (p < 0.05). All patients with monoethylglycinexylodide production less than 20 ng/ml had cirrhosis confirmed on histological examination. In contrast, no relationship was observed between liver histological status and serum transaminases (AST or ALT), bilirubin, albumin and prothrombin time. Thirty-five patients underwent repeat histological evaluation and monoethylglycinexylodide testing after receiving at least 6 mo treatment for chronic hepatitis (interferon for hepatitis B and C and corticosteroids for autoimmune hepatitis). The change in monoethylglycinexylodide production observed in these patients was a linear function of the change in Knodell histological index (r = 0.73, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hepatic lidocaine metabolism and complications of cirrhosis. Implications for assessing patient priority for hepatic transplantation.

The number of patients awaiting hepatic transplantation continues to exceed organ donation. As a result, many liver transplant candidates will develop life-threatening complications of their liver disease and not survive the pretransplant waiting period. Recent studies have demonstrated that hepatic lidocaine metabolism into monoethylglycinexylidide (MEG-X) can predict pretransplant survival. The present study was performed to determine if MEG-X could also predict pretransplant complications and thereby be useful in stratifying persons being evaluated for hepatic transplantation. A total of 57 patients with biopsy-proven cirrhosis underwent MEG-X testing. Of 57 patients, 30 (53%) developed life-threatening complications of their liver disease--i.e., variceal bleeding, grade II hepatic encephalopathy or worse, and spontaneous bacterial peritonitis. MEG-X values were greater in persons without complications of liver disease than in persons with complications (25.7 +/- 2.9 versus 14.7 +/- 1.4 ng/ml, respectively). No patients with MEG-X greater than 30 ng/ml developed a major complication. No significant difference in any of the standard liver function tests existed between persons who developed complications and patients who did not. In this group of 57 patients, 4 (7%) died from complications of cirrhosis. Mean MEG-X for patients who died (5.5 +/- 1.6 ng/ml) was significantly less (P < 0.05) than observed for other patient groups. All patients who died had MEG-X values below 10 ng/ml. This suggests that MEG-X testing could be an extremely useful test in the evaluation of patients for hepatic transplantation by identifying persons at increased risk for developing complications of chronic liver disease.

Adult↗
PubMed1993

Determination of ethylene glycol in serum utilizing direct injection on a wide-bore capillary column.

A simple, rapid, and reliable procedure for the determination of ethylene glycol (EG) and other diol compounds utilizing direct injection of diluted serum on a unique wide-bore capillary column containing a highly polar stationary phase (Nukol column) is presented. The method uses 1,4-butanediol as the internal standard (IS) and resolves propylene glycol, EG, 1,3-butanediol, and diethylene glycol. The within-run precision of the method yielded at 27.5 mg/L EG, CV = 9.4% (n = 10) and at 222 mg/L EG, CV = 7.3% (n = 10). Absolute recovery of EG at 222 mg/L was 95.9 +/- 7.1% (n = 10). At the limit of quantitation, 27.5 mg/L EG, the absolute recovery was 115 +/- 13.1% (n = 10). The method was free of interference from common volatile intoxicants, organic acid metabolites, and polar drugs. However, valproic acid was not completely resolved from the IS. The Nukol column has demonstrated an extended column lifetime and versatility for analysis of other polar compounds.

Chromatography, Gas↗
PubMed1992

Evaluation of the Vision Theophylline assays in the emergency department setting.

STUDY OBJECTIVES: To determine whether the use of fingerstick blood samples or venipuncture blood samples affect the accuracy and the precision of the Vision Theophylline I assay and the Vision Theophylline II assay in the emergency department setting. DESIGN: Prospective clinical trial. SETTING: ED in a university teaching hospital. SUBJECTS/INTERVENTIONS: Simultaneous fingerstick and venipuncture blood samples were obtained from adult patients who required baseline theophylline levels in the ED. MEASUREMENTS: The Vision system was used in the ED to measure theophylline concentrations from fingerstick and venipuncture samples. Vision samples were drawn and analyzed by one of three pharmacists rounding within the ED between March and October 1990. These pharmacists were instructed by laboratory personnel concerning pertinent operating procedures. The vision Theophylline I and Theophylline II assays are enzyme-inhibitor immunoassays contained within a multi-chamber test packet. The high-performance liquid chromatography (HPLC) theophylline assay was used as the reference method. MAIN RESULTS: Linear regression of theophylline concentrations determined by the Vision Theophylline I assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9440; P less than .05) and for venipuncture samples (r = .9750; P less than .05). The accuracy values for Vision Theophylline I assay venipuncture and fingerstick samples versus HPLC were -0.63 +/- 1.2 mg/l and 0.22 +/- 1.8 mg/L, respectively. The precision for Vision Theophylline I assay venipuncture and fingerstick samples versus HPLC were 0.27 and 0.38, respectively. Linear regression of theophylline concentrations determined by the Vision Theophylline II assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9804; P less than .05) and for venipuncture samples (r = .9875; P less than .05). Accuracy values for Vision Theophylline II fingerstick and venipuncture samples versus HPLC were -0.53 +/- 1.4 mg/L and -0.65 +/- 1.3 mg/L, respectively. Precision values for Vision Theophylline II fingerstick and venipuncture samples versus HPLC were 0.34 and 0.29, respectively. CONCLUSION: There is a strong correlation between theophylline concentrations measured by Vision Theophylline assay versus HPLC, regardless of whether the Vision Theophylline assay is performed on a fingerstick or venipuncture sample. Vision fingerstick samples were more accurate than Vision venipuncture samples for both Vision Theophylline I and II assays. Theophylline concentrations measured by the Vision system using venipuncture samples were slightly more precise than those using fingerstick samples when compared with HPLC analysis. These differences in accuracy and precision were not clinically relevant.

Blood Specimen Collection↗
PubMed1991

Determination of serum acetaminophen in emergency toxicology: evaluation of newer methods: Abbott TDx and second derivative ultraviolet spectrophotometry.

Newer methods for the determination of serum acetaminophen in emergency toxicology, the Abbott TDx immunoassay and second derivative ultraviolet spectrophotometry, were evaluated and compared to a high pressure liquid chromatographic procedure. The Abbott TDx immunoassay within-run and day to day precision yielded coefficients of variance below 2.7% and 7.2% respectively: Abbott TDx immunoassay results correlated well with those of high pressure liquid chromatographic in patient serums 15.0 to 333 mg/L acetaminophen; r2 = 0.954, n = 40. The Abbott TDx immunoassay assay was rapid, easy to perform, free of interferences from other drugs and exhibited no carryover from previous samples. The within run precision of the second derivative ultraviolet spectrophotometry method yielded coefficients of variance of less than 7.0%. Second derivative ultraviolet spectrophotometry results demonstrated good correlation with high pressure liquid chromatographic results in patient sera; r2 = 0.923, n = 40; however, performance deteriorated below 50.0 mg/L acetaminophen. Spectral interferences were noted at high concentrations of some drugs.

Acetaminophen↗
PubMedDate not supplied

Evaluation of the ETS and ADx urine drug screening immunoassay analyzers.

The Syva ETS and Abbott ADx urine drug testing immunoassay systems were evaluated for analytical performance, ease of operation, data processing, and time of analysis. Urine specimens were analyzed by each system for six drugs of abuse. Discrepancies in drug detection were due to variations in the cut-off concentrations between ADx and EMIT d.a.u. (ETS) reagents. The ETS was found to have several major advantages over the ADx: greater sample load, more convenient "random access," and real time data processing. When analyzing multiple specimens, the turnaround time for the ETS as compared to the ADx was twice as fast for the six-analyte assay. The ADx assay calibrations were stable for two weeks, while the ETS required daily calibration with verification by cut-off calibrators every eight hours. The ETS was found superior to the ADx for multianalyte urine drug screening.

Evaluation Studies as Topic↗
PubMedDate not supplied

Direct determination of benzoylecgonine in serum by EMIT d.a.u. cocaine metabolite immunoassay.

An EMIT d.a.u. immunoassay for urine testing was applied on the Syva ETS Plus analyzer for the detection of the cocaine metabolite, benzoylecgonine (BE), in human serum. Serum was analyzed without prior extraction, concentration, or matrix modification. Calibrators and serum controls were prepared from EMIT d.a.u. calibrators that were reconstituted and diluted with EMIT Tox serum calibrator. The assay cutoff concentration for BE was 50 ng/mL. The within-run and between-run precisions of the assay were both less than 5%. Analysis of 162 patient serums yielded 43 BE positive results. All EMIT positive serum BE results were confirmed by gas chromatography-mass spectrometry. All patients with positive BE serums also had BE positive urine samples. Serum bilirubin and triglycerides as high as 38 mg/dL and 319 mg/dL, respectively, did not interfere with the assay. Modification of the EMIT urine assay allowed for a simple, rapid, and reliable method for the detection of BE in serum.

Cocaine↗
PubMedDate not supplied

Preliminary report on the application of a high performance liquid chromatographic method for alprazolam in postmortem blood specimens.

A high performance liquid chromatographic (HPLC) method for the determination of alprazolam in postmortem blood specimens is described. The method is sensitive, reproducible, and gives good resolution between other benzodiazepines. Recovery of alprazolam from spiked blood specimens at 100 ng/mL was 89%. The procedure was applied to a case of suicidal ingestion of alprazolam and a blood concentration of 177 ng/mL was determined.

Adult↗