Codeine toxicology

For all 12 mother-infant pairs, either the mother or the infant s toxicology report was subsequently positive for PCP. In nine cases, the screens for both mother and infant were positive. In two cases, the mother s results were positive and the infant s were negative. In one case, the infant had a positive result while the mother s test was negative. Test sensitivity, specimen handling procedures, and delays in obtaining specimens undoubtedly contributed to the inconsistency in paired results. Cocaine, codeine, and glutethemide, in addition to phencyclidine, were identified in the urine toxicology screens of two mothers and their neonates. 

The analysis of codeine, morphine, 6-monoacetylmorphine (6-MAM, a metabohte of heroin), and cocaine is important for many toxicology labs to determine illicit drug use. When analyzing opiates in urine samples, frequently the matrix chosen for drug screening, the conjugated metabolites must be hydrolyzed however, this process can break down 6-MAM (Christophersen et al., 1987). These compounds can be derivatized to increase sensitivity, and both BCD and NPD are used for these assays. Derivatizations used include reaction with N-methyl-N-trimethylsilyltrifluoroacetamide followed by GC-FID (Lin et al., 1994) or with N,0-bis(trimethylsilyl)trifluoroacetamide (Christophersen et al., 1987 Lee and Lee, 1991), PFPA (Christophersen et al., 1987), or heptafluorobutyric anhydride (HFBA) followed by GC-ECD. All these methods show good sensitivity and selectivity. 

A 44-year-old black man developed priapism 2 hours after having overdosed on 30-40 trazodone tablets 50 mg and 10 Tylenol No. 3 (paracetamol plus codeine) tablets (162). Toxicology analysis was positive for cocaine and opiates. The priapism required detumescence twice, on initial presentation and then 6 hours later, and 8 hours after presentation he again developed painless priapism, which resolved spontaneously after 1.5 hours. 

The determination of the heroin metabolites morphine, morphine-6-glucuronide (M6G), morphine-3-glucuronide (M3G), and 6-monoacetyhnorphine (6-MAM) in body fluids is an important application of LC-MS in the toxicology laboratory. In some cases, codeine and codeine-6-glucuronide are determined as well. Several quantitative methods have been reported. However, only a few deal with forensic toxicology, performing the analysis in urine, serum, vitreous humour [79], and autopsy whole blood [79-80]. 

In the discovery phase, metabolite identification is usually performed with a combination of in vitro and in vivo experiments using samples from different species in order to compare metabolite exposures. The structural identification of major circulating metabolites formed in nonclinical animal models as well as the metabolites formed in human in vitro systems is needed for the metabolites to be synthesized and their pharmacological activities and/or toxicological implications to be determined [25], In addition, metabolite identification can lead to the discovery of candidates with satisfactory clearance/PK properties and/or improved safety profile. Following are some examples of metabolites that were later developed as drugs desloratadine from loratadine, acetaminophen from phenacetin, morphine from codeine, minoxidil sulfate from minoxidil, fexofenadine from terfenadine, and oxazepam from diazepam. 

Unlike morphine, codeine is absorbed orally. The side effects are the same as morphine s but are milder and far less frequent. Codeine produces miosis, respiratory depression, urinary retention, and constipation, but these are not of clinical or toxicological significance (see also Figure 68). 

Robinson (12) wrote a review on the metabolism and function of alkaloids in plants in which references to morphine, codeine, and thebaine were given. Preininger (13) published a comprehensive review including 691 references on the pharmacology and toxicology of the Papaveraceae alkaloids. 

Coles, R., M. M. Kushnir, G. J. Nelson, A. Gwendolyn, cuid F. M. Urry. 2007. Simultaneous determination of codeine, morphine, hydrocodone hydromor-phone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS/MS. Journal of Analytical Toxicology 31 (1) 1-14. Drummer, O. H. 2004. Postmortem toxicology of abused drugs. Forensic Science International 142 (2-3) 101-113. 

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