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1.
J Anal Toxicol ; 33(3): 148-54, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19371463

ABSTRACT

The results of meconium specimens and fortified samples screened for drugs of abuse by both enzyme multiplied immunoassay technique (EMIT((R) )II) and enzyme-linked immunosorbent assay (ELISA) methods were compared. The sample preparation for the ELISA screen was a simple buffer extraction versus a lengthy and more laborious sample preparation procedure for the EMIT II screen. The ELISA method was automated using a TECAN Genesis. The EMIT II analysis was automated with an Olympus AU400e. The opioid screen was calibrated with hydromorphone and the benzodiazepine screen was calibrated with clonazepam to maximize detection for these analytes. Previously validated gas chromatography-mass spectrometry (GC-MS), two-dimensional GC-MS, or liquid chromatography-tandem MS methods were used for confirmation. Results from the two techniques compared well. Agreement of the ELISA assay was greater than 90% when compared to EMIT II for all drug classes except barbiturates and benzodiazepines. ELISA appears to be more sensitive than EMIT II for the detection of amphetamines, methadone, propoxyphene, and cocaine. ELISA compared well to EMIT II for cannabinoids, opioids, and PCP. Specificity of the ELISA assay was slightly better for PCP and opioids. EMIT II appears to be more sensitive for the detection of barbiturates and benzodiazepines. The ELISA method reduced turnaround time by 50% compared to the EMIT II method.


Subject(s)
Enzyme Multiplied Immunoassay Technique , Enzyme-Linked Immunosorbent Assay/methods , Illicit Drugs/analysis , Meconium/chemistry , Substance Abuse Detection/methods , Substance-Related Disorders/diagnosis , Amphetamines/analysis , Analgesics, Opioid/analysis , Barbiturates/analysis , Benzodiazepines/analysis , Cannabinoids/analysis , Chromatography, Liquid , Cocaine/analysis , Dextropropoxyphene/analysis , False Positive Reactions , Female , Fetus/metabolism , Gas Chromatography-Mass Spectrometry , Humans , Infant, Newborn , Maternal-Fetal Exchange/physiology , Methadone/analysis , Phencyclidine Abuse/diagnosis , Pregnancy , Sensitivity and Specificity , Tandem Mass Spectrometry
2.
J Anal Toxicol ; 32(9): 787-9, 2008.
Article in English | MEDLINE | ID: mdl-19021937

ABSTRACT

Dextropropoxyphene (DP) and norpropoxyphene (NP) are commonly used in the treatment of postpartum pain. The drug is widely prescribed in Europe and Canada and has been recently approved for use in the U.S. Its safety during breastfeeding, however, has not been fully established. Very few reports on its effects on neonates have been published. We report here the case of a mother treated with DP (6 capsules a day for 10 days) while she was breastfeeding. On day 7, her baby was lethargic and had difficulties with breastfeeding, which led to early weaning. The correlation between side effects observed in the infant and DP was made retrospectively by measuring DP and NP hair concentrations in the mother-infant pair with liquid chromatography-tandem mass spectrometry. Breastfeeding mothers taking DP expose their infants to high doses of DP and NP. In agreement with previously published reports, these data indicate that acetaminophen and nonsteroidal antiinflammatories are preferable for analgesia during breastfeeding. Breastfeeding should be encouraged under most circumstances, and if the mother takes any treatment for pain, a commonly prescribed drug with pharmacologic data available must be used.


Subject(s)
Analgesics, Opioid/adverse effects , Analgesics, Opioid/analysis , Breast Feeding , Dextropropoxyphene/analogs & derivatives , Dextropropoxyphene/adverse effects , Dextropropoxyphene/analysis , Hair/chemistry , Adult , Chromatography, High Pressure Liquid , Female , Humans , Infant, Newborn , Pain/drug therapy , Postpartum Period , Pregnancy , Retrospective Studies , Tandem Mass Spectrometry
3.
J Forensic Leg Med ; 15(6): 395-7, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18586212

ABSTRACT

We encountered a decedent with an unexpected glioblastoma multiforme. A 61-year-old retired African-American woman was found dead in her home, fully clothed in her bathtub, with a pillow under her head. At autopsy, the brain showed a glioblastoma multiforme. Toxicology showed elevated hydrocodone, propoxyphene, acetaminophen, and positive paroxetine. The presence of a brain tumor likely caused a severe headache. The use of her medications could have indicated a reaction to the escalating pain of the brain trauma, and overuse could be consistent with escalating pain or loss of rational thought processes. The present case is interesting in that it had evidence of behavioral dysfunction that could be related to the brain tumor, and death arising from the glioblastoma multiforme (cerebral hemorrhage and edema) with concurrent multiple drug intoxication.


Subject(s)
Brain Neoplasms/pathology , Glioblastoma/pathology , Headache Disorders, Secondary/drug therapy , Mental Disorders/etiology , Self Medication/adverse effects , Acetaminophen/administration & dosage , Acetaminophen/adverse effects , Acetaminophen/analysis , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Analgesics, Non-Narcotic/analysis , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Analgesics, Opioid/analysis , Brain Edema/etiology , Brain Edema/pathology , Brain Neoplasms/complications , Dextropropoxyphene/administration & dosage , Dextropropoxyphene/adverse effects , Dextropropoxyphene/analogs & derivatives , Dextropropoxyphene/analysis , Female , Forensic Pathology , Forensic Toxicology , Glioblastoma/complications , Headache Disorders, Secondary/etiology , Humans , Hydrocodone/administration & dosage , Hydrocodone/adverse effects , Hydrocodone/analysis , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/pathology , Middle Aged , Paroxetine/administration & dosage , Paroxetine/adverse effects , Paroxetine/analysis , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/analysis , Vitreous Body/chemistry
4.
Forensic Sci Int ; 176(1): 47-50, 2008 Mar 21.
Article in English | MEDLINE | ID: mdl-18006260

ABSTRACT

This article discusses the immunoassay screening of pain management drugs, and the mass spectrometric confirmation of fentanyl in human hair. Hair specimens were screened for fentanyl, opiates (including oxycodone), tramadol, propoxyphene, carisoprodol, methadone, and benzodiazepines and any positive results were confirmed using gas chromatography or liquid chromatography with mass spectral detection. The specific focus of the work was the determination of fentanyl in hair, since autopsy specimens were also available for comparison with hair concentrations. Using two-dimensional gas chromatography with electron impact mass spectrometric detection, fentanyl was confirmed in four of nine hair specimens collected at autopsy. The accuracy of the assay at 10 pg/mg was 95.17% and the inter-day and intra-day precision was 5.04 and 13.24%, respectively (n=5). The assay was linear over the range 5-200 pg/mg with a correlation of r(2)>0.99. The equation of the calibration curve forced through the origin was y=0.0053x and the limit of quantitation of the assay was 5 pg/mg. The fentanyl concentrations detected were 12, 17, 490, and 1930 pg/mg and the results were compared with toxicology from routine post-mortem analysis. The screening of pain management drugs in hair is useful in cases where other matrices may not be available, and in routine testing of hair for abused drugs.


Subject(s)
Analgesics, Opioid/analysis , Fentanyl/analysis , Hair/chemistry , Benzodiazepines/analysis , Carisoprodol/analysis , Dextropropoxyphene/analysis , Enzyme-Linked Immunosorbent Assay , Forensic Toxicology , Gas Chromatography-Mass Spectrometry , Humans , Methadone/analysis , Oxycodone/analysis , Substance Abuse Detection , Tramadol/analysis
5.
J Anal Toxicol ; 30(8): 516-8, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17132245

ABSTRACT

The determination of propoxyphene in oral fluid using solid-phase extraction and gas chromatography-mass spectrometry is described for the first time. The method employs collection of oral fluid with the Quantisal device, immunoassay screening of the specimen, confirmation of the positive screened samples after extraction using cation exchange/hydrophobic solid-phase extraction columns, optimized derivative formation, and gas chromatography-mass spectrometry in electron impact mode. Validated parameters including selectivity, linearity, accuracy, intra- and interday precision, extraction efficiency, and limit of quantitation were all within acceptable limits. The method was applied to authentic specimens taken from an individual prescribed propoxyphene following surgery.


Subject(s)
Dextropropoxyphene/analysis , Gas Chromatography-Mass Spectrometry/methods , Narcotics/analysis , Saliva/chemistry , Adult , Dextropropoxyphene/immunology , Female , Forensic Toxicology/methods , Humans , Immunoassay , Narcotics/immunology , Reproducibility of Results , Saliva/immunology , Sensitivity and Specificity
6.
Anal Bioanal Chem ; 376(6): 838-43, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12802564

ABSTRACT

An improvement is presented on the simultaneous determination of two active ingredients present in unequal concentrations in injections. The analysis was carried out with spectrophotometric data and non-linear multivariate calibration methods, in particular artificial neural networks (ANNs). The presence of non-linearities caused by the major analyte concentrations which deviate from Beer's law was confirmed by plotting actual vs. predicted concentrations, and observing curvatures in the residuals for the estimated concentrations with linear methods. Mixtures of dextropropoxyphene and dipyrone have been analysed by using linear and non-linear partial least-squares (PLS and NPLSs) and ANNs. Notwithstanding the high degree of spectral overlap and the occurrence of non-linearities, rapid and simultaneous analysis has been achieved, with reasonably good accuracy and precision. A commercial sample was analysed by using the present methodology, and the obtained results show reasonably good agreement with those obtained by using high-performance liquid chromatography (HPLC) and a UV-spectrophotometric comparative methods.


Subject(s)
Dextropropoxyphene/analysis , Dipyrone/analysis , Neural Networks, Computer , Pharmaceutical Preparations/analysis , Anti-Inflammatory Agents, Non-Steroidal/analysis , Antitussive Agents/analysis , Computer Simulation , Electrochemistry , Molecular Structure , Nonlinear Dynamics , Pharmaceutical Preparations/chemistry
8.
J Chromatogr B Biomed Sci Appl ; 709(1): 69-77, 1998 May 08.
Article in English | MEDLINE | ID: mdl-9653927

ABSTRACT

After conversion of norpropoxyphene (NP) to its corresponding amide, dextropropoxyphene (DP) and NP are extracted from 1 ml of blood or 50 mg of powdered hair, on C18 cartridges and eluted using methanol containing 0.5% acetic acid. Automated extraction is conducted on-line with automated device, starting from buffered and centrifuged sample. After extraction, the dried residue is reconstituted with 40 microl of methanol, and then injected in a gas chromatograph at 250 degrees C. Quantitation is carried out by gas chromatography-mass spectrometry in the selected-ion monitoring mode, lidocaine being the internal standard. The method gave relative standard deviations lower than 6.2% in whole blood, and 6.0% in hair for the entire range of calibration from 0.5 to 10 microg/ml in blood and from 1 to 20 ng/mg in hair of both compounds. Limits of detection in blood and hair for DP are, respectively, 0.07 microg/ml and 0.05 ng/mg, whereas the respective limits of detection in whole blood and hair for NP are 0.09 microg/ml and 0.04 ng/mg. The present method was used for one year in our laboratory. Postmortem concentrations of DP in blood ranged from 1.6 to 44.0 microg/ml (mean=9.8microg/ml, n = 12) and are comparable to those found in the literature. Out of 30 hair samples from people who died from heroin overdose, 13 were positive both for DP and NP with concentrations ranging from 0.2 to 27.4 ng/mg (mean 8.7 ng/mg) for DP and 0.3 to 68.9 ng/mg (mean 24.1 ng/mg) for NP.


Subject(s)
Analgesics, Opioid/analysis , Dextropropoxyphene/analogs & derivatives , Dextropropoxyphene/analysis , Gas Chromatography-Mass Spectrometry/methods , Hair/chemistry , Adult , Analgesics, Opioid/blood , Automation , Dextropropoxyphene/blood , Drug Overdose/metabolism , Forensic Medicine , Heroin Dependence/metabolism , Humans , Male , Sensitivity and Specificity , Substance-Related Disorders/metabolism
9.
J Chromatogr B Biomed Sci Appl ; 706(2): 245-51, 1998 Mar 20.
Article in English | MEDLINE | ID: mdl-9551810

ABSTRACT

The identification of four doping control substances in an artificial mixture, using short column gas chromatography-mass spectrometry (GC-MS) analysis was examined. Two chromatographic peaks were recorded in the chromatogram, using a short capillary column (1.8 m) at an oven temperature of 180 degrees C. The first peak was associated with a mixture of a solvent derivative and an artifact. The second one corresponded to the mixture of four control substances. Principal component analysis was applied on a selected GC-MS data set of the latter peak to determine clear full spectra of pure substances from mixture spectra. The time of GC-MS analysis was significantly reduced to less than 1 min from 30 min which is a typical GC-MS analysis time, using standard methods of doping control analysis.


Subject(s)
Gas Chromatography-Mass Spectrometry/methods , Narcotics/analysis , Substance Abuse Detection/methods , Cocaine/analysis , Dextromethorphan/analysis , Dextropropoxyphene/analysis , Factor Analysis, Statistical , Methadone/analysis , Software , Time Factors
10.
Ann Clin Biochem ; 34 ( Pt 5): 460-510, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9293303

ABSTRACT

Requirements for the provision of an efficient and reliable service for drugs of abuse screening in urine have been summarized in Part I of this review. The requirements included rapid turn-around times, good communications between requesting clinicians and the laboratory, and participation in quality assessment schemes. In addition, the need for checking/confirmation of positive results obtained for preliminary screening methods was stressed. This aspect of the service has assumed even greater importance with widespread use of dip-stick technology and the increasing number of reasons for which drug screening is performed. Many of these additional uses of drug screening have possible serious legal implications, for example, screening school pupils, professional footballers, parents involved in child custody cases, persons applying for renewal of a driving licence after disqualification for a drug-related offence, doctors seeking re-registration after removal for drug abuse, and checking for compliance with terms of probation orders; as well as pre-employment screening and work-place testing. In many cases these requests will be received from a general practitioner or drug clinic with no indication of the reason for which testing has been requested. This also raises the serious problems of a chain of custody, provision of two samples, stability of samples, and secure and lengthy storage of samples in the laboratory-samples may be requested by legal authorities several months after the initial testing. The need for confirmation of positive results is now widely accepted but it may be equally important to confirm unexpected negative results. Failure to detect the presence of maintenance drugs may lead to the patient being discharged from a drug treatment clinic and, if attendance at the clinic is one of the terms of continued employment, to dismissal. It seems likely that increasing abuse of drugs and the efforts of regulatory authorities to control this, will lead to the manufacture of more designer drugs. Production of substituted phenethylamines was facilitated by the drug makers' cook book, 'PIHKAL' (Phenethylamines I Have Known And Loved) by Dr Alexander Shulgin and Ann Shulgin, and production of substituted tryptamines is promised in their next book, TIHKAL. Looking to the future, laboratories will need to ensure that they can detect and quantitate an ever-increasing number of drugs and related substances. The question of confidence in results of drugs of abuse testing raised in 1993 by Watson has assumed even greater importance as a result of attention focused on the OJ Simpson trial in Los Angeles. Toxicological investigations are likely to be challenged more frequently in the future. Even if analyses have been performed by GC-MS, there is a need to establish the level of match between the spectrum of the unknown substance and a library spectrum which is considered acceptable for legal purposes. It will also be essential to ensure that computer libraries contain spectra for all substances likely to be encountered in drugs of abuse screening.


Subject(s)
Barbiturates/urine , Buprenorphine/urine , Cannabinoids/urine , Lysergic Acid Diethylamide/urine , Substance Abuse Detection/methods , Benzodiazepines/blood , Benzodiazepines/urine , Buprenorphine/blood , Cyclizine/analysis , Dextropropoxyphene/analysis , Drug Combinations , Fentanyl/urine , Humans , Ketamine/blood , Ketamine/urine , Methadone/analogs & derivatives , Methadone/analysis , Methadone/blood , Methadone/urine , Pentazocine/analysis
11.
Bioconjug Chem ; 8(3): 385-90, 1997.
Article in English | MEDLINE | ID: mdl-9177845

ABSTRACT

The synthesis of [S-(R,S)]-4-[[methyl[2-methyl-3-(1-oxopropoxy)-3, 4-diphenylbutyl]amino]-1-oxobutoxy]-2,5-pyrrolidinedione+ ++ (propoxyphene active ester, 2) is described. This was used as an intermediate to prepare a propoxyphene immunogen, [S-(R,S)]-4-[methyl][2-methyl-3-(1-oxopropoxy)-3,4-diphenylbuty l]-amino]- 1-oxobutyl-Bovine Thyroglobulin (3). This immunogen was then used to generate antibodies which demonstrate good cross-reactivity to d-propoxyphene, d-norpropoxyphene, and other propoxyphene metabolites. In addition, these antibodies were shown to have very low cross-reactivity to methadone, a structurally related compound. The introduction of an aminomethyl benzoate spacer into the propoxyphene active ester (2), followed by the activation of the carboxylic acid, provided for a more stable active ester (5). This stable active ester, together with the antibodies generated from the propoxyphene immunogen, has led to the development of an immunoassay based on the Kinetic Interaction of Microparticles in Solution (KIMS).


Subject(s)
Dextropropoxyphene/analogs & derivatives , Dextropropoxyphene/analysis , Narcotics/analysis , Animals , Cross Reactions , Dextropropoxyphene/immunology , Humans , Sheep
12.
Forensic Sci Int ; 84(1-3): 237-42, 1997 Jan 17.
Article in English | MEDLINE | ID: mdl-9042729

ABSTRACT

Hair samples taken from 11 persons suspected to have died from an overdose of legal or illicit drugs were analysed. These hair samples were selected, because classical post-mortem toxicological investigations in blood revealed the presence of dextropropoxyphene (PPX) and its major metabolite norpropoxyphene (NPPX). For the hair analysis, hair strands were cut into segments of about 3 cm, washed with water and acetone, dried and pulverised. An aliquot of about 40 mg of those segments was incubated with acetate buffer pH 4.0 and beta-glucuronidase/arylsulfatase. After liquid-liquid extraction with hexane-3-methylbutanol (99:1), drugs were identified and measured by HPLC using piritramide as an internal standard. Preliminary assays showed that the limit of detection for PPX is below 1.0 ng/mg hair, the limit of detection for the metabolite NPPX being significantly higher (1.5 ng/mg). GC/MS, usually the method of choice for this kind of determination, was not chosen, because of the thermolability of PPX and its unspecific mass spectrum. From the hair of 11 persons, 24 segments were prepared and processed. Our results show that ten persons were found positive for PPX; moreover, when regarding the 24 segments, only three were found negative. PPX and NPPX concentrations were detected at maximal concentrations of 26.4 and 71.0 ng/mg hair respectively. Considering the ratio of PPX to NPPX for each person, we found more PPX than NPPX for three persons, whereas for seven persons we found more of the metabolite than its parent drug.


Subject(s)
Chromatography, High Pressure Liquid/methods , Dextropropoxyphene/analysis , Hair/chemistry , Narcotics/analysis , Drug Overdose/blood , Drug Overdose/urine , Humans , Substance Abuse Detection/methods , Substance-Related Disorders/blood , Substance-Related Disorders/urine
13.
J Anal Toxicol ; 20(7): 537-40, 1996.
Article in English | MEDLINE | ID: mdl-8934302

ABSTRACT

A study was conducted to compare the clinical sensitivity of the OnLine and EMIT II assays for propoxyphene (PPX) use in human urine. A total of 5138 random clinical samples were evaluated by both OnLine and EMIT II. Samples that were positive for each immunoassay were confirmed for PPX and norpropoxyphene (NPPX) by gas chromatography-mass spectrometry (GC-MS). There were 14 samples that were identified positive by both immunoassays and confirmed positive by GC-MS. An additional six samples were positive by OnLine, negative by EMIT II, and confirmed positive by GC-MS. There was one unconfirmed positive sample identified by each immunoassay, and 5116 samples were identified as negative by both immunoassays. The increased sensitivity by OnLine can be attributed to the cross reactivity of the OnLine antibody, which is higher than the cross reactivity of the EMIT II antibody for NPPX (77% versus 7%, respectively). The high concentrations of NPPX, relative to those of PPX, found in all of the clinical samples suggest that laboratories that currently confirm for PPX should confirm for NPPX in order to obtain a better correlation between immunoassay results and GC-MS confirmations.


Subject(s)
Analgesics, Opioid/analysis , Dextropropoxyphene/analogs & derivatives , Dextropropoxyphene/analysis , Gas Chromatography-Mass Spectrometry/methods , Immunoassay/methods , Reagent Kits, Diagnostic , Dextropropoxyphene/immunology , Humans , Sensitivity and Specificity , Substance Abuse Detection/methods
14.
J Anal Toxicol ; 17(4): 222-4, 1993.
Article in English | MEDLINE | ID: mdl-8371551

ABSTRACT

This study evaluated the capability of the Abbott TDx assay to test for propoxyphene in urine and various biological samples, including tissues obtained from three fatal overdoses, by comparison to gas chromatography/mass spectrometry (GC/MS). First, within-run and between-run precision were determined using three control samples (200, 400, and 900 ng/mL) tested over a two-week period. Within-run coefficients of variation (CV) for the three controls were 1.4, 2.2, and 2.5%, respectively; the between-run CVs were 2.5, 3.1, and 4.0%, respectively. The cross-reactivity with norpropoxyphene, the major metabolite of propoxyphene, was concentration dependent and in the range of 29.3 to 92.6%. Propoxyphene and its metabolite were assayed in biological samples the same day using the Abbott TDx and GC/MS. Tissue preparations were analyzed by TDx without specimen pretreatment other than homogenization and dilution with saline. The TDx results were in accordance with the results obtained by GC/MS.


Subject(s)
Dextropropoxyphene/analysis , Fluorescence Polarization Immunoassay , Gas Chromatography-Mass Spectrometry , Dextropropoxyphene/urine , Evaluation Studies as Topic , Humans , Reagent Kits, Diagnostic
15.
Am J Forensic Med Pathol ; 14(2): 118-20, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8328429

ABSTRACT

We reared larvae of Calliphora vicina on human skeletal muscle obtained from cases of suicidal overdose with co-proxamol (propoxyphene and acetaminophen) and amitriptyline. After 4 days, third-instar larvae were either transferred to drug-free muscle or continued to feed on drug-laden muscle for a further 2 days prior to harvesting. Amitriptyline and nortriptyline were detected in both groups of larvae, but propoxyphene was only in those fed continuously on drug-laden muscle, and acetaminophen was in neither. Drug concentrations in muscle food source were amitriptyline 0.48 microgram/g, nortriptyline 0.38 microgram/g, propoxyphene 0.99 microgram/g, and acetaminophen 14.13 micrograms/g. For triplicate rearings, the mean ratios of drug concentrations in larvae to food source were amitriptyline, 0.56; nortriptyline, 0.5; and propoxyphene, 0.06. In triplicate rearings, no drug or metabolite was detected in puparia, puparial cases, or imagos. We conclude that the absence of a drug in maggots is not necessarily an indication that the drug was not present in significant concentrations in the food source. The malpighian tubules and the "nephrocytes" of fly larvae appear capable of eliminating different drugs with varying efficiency.


Subject(s)
Acetaminophen/analysis , Amitriptyline/analysis , Dextropropoxyphene/analysis , Diptera/chemistry , Forensic Medicine , Acetaminophen/poisoning , Amitriptyline/poisoning , Animals , Dextropropoxyphene/poisoning , Diptera/growth & development , Drug Combinations , Drug Overdose , Humans , In Vitro Techniques , Larva/chemistry , Muscles , Pupa/chemistry , Suicide
16.
Forensic Sci Int ; 57(2): 147-56, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1473806

ABSTRACT

In three instances of suicidal poisoning by co-proxamol (paracetamol and dextropropoxyphene) blood samples were obtained from 11 sites together with eight tissue samples, bile, urine, gastric contents and duodenal contents. Site-dependent differences in blood propoxyphene concentration varied between the three cases but concentrations were consistently lowest in peripheral blood and highest in central sites: 3.9-5.5 (pulmonary vein) mg/l; 4.6-25 (pulmonary vein) mg/l; 3.2-40 (aorta) mg/l. There was a less than twofold variation in corresponding blood paracetamol concentrations. Reference data on fatal propoxyphene blood concentrations do not specify the blood sampling site and can be misleading. The intra-individual variability of propoxyphene concentrations in blood in these three cases underscores this problem. Tissue concentrations of propoxyphene showed considerable inter-individual variability in degree and pattern. Tissue concentrations of paracetamol showed a less than twofold intra-individual variation. Body drug loads were calculated by two methods: from organ weights and tissue concentrations; from published volume of distribution data (Vd). For paracetamol the body drug load is underestimated by the organ weight calculation but the Vd calculation approximates the suspected dose based on anamnestic information. For propoxyphene the body drug load is seriously underestimated by the organ weight calculation and overestimated up to 2.5 times by the Vd calculation. Since the two drugs have a fixed ratio in co-proxamol then the dose of propoxyphene (the effective lethal agent) can be inferred from the paracetamol dose calculated by Vd. This approach may be applicable to cases of overdose with other compounded drug preparations.


Subject(s)
Acetaminophen/poisoning , Dextropropoxyphene/poisoning , Suicide , Acetaminophen/administration & dosage , Acetaminophen/analysis , Adolescent , Adult , Body Fluids/chemistry , Dextropropoxyphene/administration & dosage , Dextropropoxyphene/analysis , Drug Combinations , Drug Overdose , Female , Gastrointestinal Contents/chemistry , Humans , Liver/chemistry , Liver/pathology , Lung/chemistry , Lung/pathology , Muscles/chemistry , Muscles/pathology , Organ Size
17.
J Forensic Sci ; 36(1): 60-9, 1991 Jan.
Article in English | MEDLINE | ID: mdl-2007881

ABSTRACT

In a random group of medical examiner cases, muscle tissue, as well as blood and vitreous humor, was analyzed for ethyl alcohol, and the results were compared. When the blood concentration was greater than 0.10 g/dL, the muscle to blood ratio was 1.00 or less (average 0.94), and when the blood concentration was less than 0.10 g/dL, this ratio was greater than 1.00 (average 1.48). The author proposes that this ratio is dependent upon the time course of absorption and distribution, as has been observed for vitreous humor, but with a more rapid equilibration. Muscle tissue was also analyzed in another group of cases found to be positive for one or more drugs in blood. The concentrations of the drugs in muscle varied from none detected to 6.5 times those in blood and seemed to be dependent on the time course between ingestion and death, as well as on the nature of the drug. For most common basic drugs, the ratios were often near unity. Muscle is proposed as a useful alternative specimen to postmortem blood.


Subject(s)
Ethanol/analysis , Muscles/chemistry , Pharmaceutical Preparations/analysis , Antidepressive Agents, Tricyclic/analysis , Antidepressive Agents, Tricyclic/blood , Benzodiazepines/analysis , Benzodiazepines/blood , Cocaine/analysis , Cocaine/blood , Codeine/analysis , Codeine/blood , Dextropropoxyphene/analysis , Dextropropoxyphene/blood , Ethanol/blood , Humans , Morphine/analysis , Morphine/blood , Postmortem Changes , Vitreous Body/chemistry
19.
J Forensic Sci Soc ; 29(3): 219-23, 1989.
Article in English | MEDLINE | ID: mdl-2794915

ABSTRACT

The analyses of bone marrow and body tissue (adipocere) from a severely decomposed body for the presence of paracetamol and dextropropoxyphene (Distalgesic) are described, and the levels of drugs found are presented. The level of dextropropoxyphene in the bone marrow was found to be unexpectedly higher than that of paracetamol.


Subject(s)
Acetaminophen/analysis , Bone Marrow/analysis , Dextropropoxyphene/analysis , Muscles/analysis , Postmortem Changes , Humans , Male , Middle Aged
20.
J Chromatogr ; 455: 279-89, 1988 Nov 25.
Article in English | MEDLINE | ID: mdl-3235615

ABSTRACT

A normal-phase high-performance liquid chromatographic method, using a 3.3 cm x 4.6 mm silica column (3 microns packing) and an ammonium hydroxide-methanol-dichloromethane mobile phase, has been developed to separate propoxyphene and acetaminophen in less than 5 min. Quantitative recovery of both compounds from various pharmaceutical preparations was achieved, following a single dilution scheme. The method is stable, reproducible, and selective.


Subject(s)
Acetaminophen/analysis , Dextropropoxyphene/analysis , Chromatography, High Pressure Liquid , Spectrophotometry, Ultraviolet
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