Unconjugated Morphine in Blood by Radioimmunoassay and Gas Chromatography/Mass Spectrometry

Spiehler, Vina; Brown, Richard S.

doi:10.1520/jfs12402j

Cited by 65 publications

(31 citation statements)

References 15 publications

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“…Furthermore, this ratio was always greater than 50%, which from consideration of the pharmacokinetics [2] indicates a rapid death in less than three hours. It is also interesting to note that in 30 of these 44 cases (68.2%), the drug material was found near the body.…”

Section: Resultsmentioning

confidence: 93%

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Morphine in postmortem blood: its importance for the diagnosis of deaths associated with opiate addiction

1990

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This article describes an analytical method for the determination of morphine, the active metabolite of heroin, in post-mortem blood by HPLC with electrochemical detection. An extraction technique allowing the determination of free and total morphine (free morphine + morphine glucuronide) was used. Blood morphine levels in postmortem cases are reported and the ratio of free to total morphine was measured in 52 cases obtained at autopsy. The importance of this ratio is discussed in relation to the circumstances of the death.

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Section: Resultsmentioning

confidence: 93%

“…Spiehler and Brown [2] have recently shown that the ratio of free to total morphine in blood could be used to estimate the time elapsed since the injection of heroin.…”

Section: Introductionmentioning

confidence: 99%

Morphine in postmortem blood: its importance for the diagnosis of deaths associated with opiate addiction

1990

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“…1 Codeine is metabolized by several mechanisms (discussed below), and the metabolites can be analyzed either as the total (the combined free drug plus the hydrolyzed conjugates) or the free drug alone. The difference between the total and free drug concentrations equals the amount of conjugated drug.…”

Section: Autopsy and Toxicology Resultsmentioning

confidence: 99%

Codeine Intoxication in the Neonate

Magnani

Evans

1999

Pediatrics

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ABSTRACT. Although opiates can provide patients with relief from pain and the discomfort of cough, the routine prescription of these drugs for infants demands caution and concern. Infants, particularly neonates, are not merely small adults requiring smaller dosages, but rather uniquely different patients. Neonates present with an immature physiology and biochemistry with respect to drug metabolism. We report a case of codeine intoxication in the neonate, in which the drug was prescribed for cough control during an emergency department visit. Pediatrics 1999;104(6). URL: http://www.pediatrics.org/ cgi/content/full/104/6/e75; codeine, neonate, toxicity, morphine, fatality. CASE REPORT Baby Z was born at 36 weeks' gestation with Apgar scores of 9 and 9. By examination he seemed to be a healthy 36-week infant with a birth weight of 6 pounds. He progressed satisfactorily and was discharged to home 2 days later.At 29 days of age, baby Z was brought to the local hospital for evaluation of frequent cough and occasional vomiting, which had started the previous day. Physical examination at that time revealed a rectal temperature of 98.2°F, a pulse of 160, and respirations of 32. A chest radiograph showed no evidence of active cardiac or pulmonary pathology and the infant was diagnosed with an upper respiratory infection. Baby Z was discharged to home with instructions to treat with Triaminic syrup (Sandoz Consumer, East Hanover, NJ) and Pedialyte (Ross Laboratories, Columbus, OH).The baby did not improve over the course of the day and returned to the hospital emergency department later that afternoon. Physical examination revealed a temperature of 97°F, a pulse of 160, and respirations of 28. The chest was clear, the heart was in normal sinus rhythm, and the abdomen was soft. The assessment at this time was a viral tracheitis. The patient was discharged to home with instructions to take 1 mL Novahistine DH (SmithKline Beecham Pharmaceuticals, Pittsburgh, PA) every 6 hours for 3 days (Novahistine DH contains 2 mg of codeine per milliliter, and in this infant, the dose would have been .63 mg/kg), to discontinue the Triaminic medication, and to see the pediatrician in 2 days.At 8 pm the baby was given a 1-mL dose of oral Novahistine DH. At 2 am on the next day, a second 1-mL dose was given. At 3 am, the baby seemed to be in no distress according to the mother. At 4 am, the mother noted that the baby was unusually quiet and when she checked, the baby was not breathing. An ambulance was called, and the baby was transported to the hospital, where resuscitative efforts continued in the emergency department. Despite lifesaving measures, the patient died. Autopsy and Toxicology ResultsNotable findings at autopsy included severe bronchitis/bronchiolitis and mild bilateral pulmonary congestion.Codeine and metabolites in postmortem samples of blood, urine, and liver extract were identified and quantitated by gas chromatography, mass spectrometry.1 Codeine is metabolized by several mechanisms (discussed below), and the metabolites can...

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“…below or similar to those of living consumers or intoxicated heroin users [3,7]. Some authors have studied the ratio of "free" to "total" morphine, in order to correlate this value with the time of death or the influence of other misused drugs [11][12][13]. "Free" morphine stands for un-conjugated morphine, while "total" morphine refers to the amount of morphine which is determined after application of a hydrolysis step to the sample.…”

Section: Introductionmentioning

confidence: 99%

Study of the Ratio between Morphine-3-β-D-Glucuronide and Morphine-6-β-DGlucuronide in Blood Samples from Heroin Fatalities

Froldi¹,

Guerrini²,

Argo³

et al. 2015

J Anal Bioanal Tech

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In heroin fatalities the diagnosis of the cause of death, based only on chemical and toxicological data, may be particularly difficult; a complete knowledge of the case history is fundamental. Thus, for each case analytical results should be interpreted taking into account also autopsy findings, information from the scene and relevant medical history. In fact wide variability is present in post-mortem blood concentration of morphine (MOR), the main metabolite of heroin, which is usually the most important analytical result for the interpretation of the cause of death. Recently, increasing interest has grown towards the role of the metabolites morphine-3-β-D-glucuronide (M3G) and morphine-6-β-D-glucuronide (M6G) in mediating heroin effects. To this purpose SPE technique was employed to extract MOR, M3G and M6G from autopsy blood samples. Subsequently a LC/MS-MS method for the determination of these analytes was developed, using a gradient elution with a binary mobile phase, the analytes being revealed by means of an ESI-QqQ Mass Spectrometer operating in positive ionization and MRM mode. After validation, the method was applied to twenty-one blood specimens collected from cases of suspected acute narcotism which previously underwent a Systematic Toxicological Analysis (STA) to highlight the presence of ethanol and of the main drugs of abuse and/or their metabolites. The concentration ratios of MOR, M3G and M6G were investigated. The influence of some risk factors, such as the contemporary use of alcohol, methadone or cocaine, was also studied. Some important indications emerged: the ratio M3G/M6G, being quite constant, should be a valid reference value to assess toxicity. Furthermore the value of M3G/M6G ratio detected in heroin addict, in this study, is lower than that found in people who assume morphine for therapeutic purposes. This ratio could be of help to overcome the difficult interpretation of chemical and toxicological data.

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Unconjugated Morphine in Blood by Radioimmunoassay and Gas Chromatography/Mass Spectrometry

Cited by 65 publications

References 15 publications

Morphine in postmortem blood: its importance for the diagnosis of deaths associated with opiate addiction

Morphine in postmortem blood: its importance for the diagnosis of deaths associated with opiate addiction

Codeine Intoxication in the Neonate

Study of the Ratio between Morphine-3-β-D-Glucuronide and Morphine-6-β-DGlucuronide in Blood Samples from Heroin Fatalities

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