J Anal Toxicol. Oct;34(8) Evaluating the relationship between postmortem and antemortem morphine and codeine concentrations in whole blood. The codeine to morphine concentration ratio is used in forensic toxi- cology to .. Tolliver et al. examined the relationship between ante- and. Analytical tests for codeine, morphine, and heroin and their applications to To improve correlation between cutoff concentrations of total morphine and 6-AM.
Related to codeine in other ways are codoximethebaconcodeine-N-oxide genocodeinerelated to the nitrogen morphine derivatives as is codeine methobromide, and heterocodeinewhich is a drug six times stronger than morphine and 72 times stronger than codeine due to a small re-arrangement of the molecule, viz.
Drugs bearing resemblance to codeine in effects due to close structural relationship are variations on the methyl groups at the 3 position including ethylmorphine a. While having no narcotic effects of its own, the important opioid precursor thebaine differs from codeine only slightly in structure.
Pseudocodeine and some other similar alkaloids not currently used in medicine are found in trace amounts in opium as well.
History[ edit ] Codeine, or 3-methylmorphine, is an alkaloid found in the opium poppyPapaver somniferum var.
Opium poppy has been cultivated and utilized throughout human history for a variety of medicinal analgesic, anti-tussive and anti-diarrheal and hypnotic properties linked to the diversity of its active components, which include morphine, codeine and papaverine. Until the beginning of the 19th century, raw opium was used in diverse preparations known as laudanum see Thomas de Quincey 's Confessions of an English Opium-Eaterand paregoric elixirsa number of which were popular in England since the beginning of the 18th century; the original preparation seems to have been elaborated in Leidenthe Netherlands around by a chemist named Lemort; in the London Pharmacopoeia mentions an Elixir Asthmaticum, replaced by the term Elixir Paregoricum "pain soother" in The progressive isolation of opium's several active components opened the path to improved selectivity and safety of the opiates-based pharmacopeia.
Codeine is the most widely used opiate in the world,   and is one of the most commonly used drugs overall according to numerous reports by organizations including the World Health Organization and its League of Nations predecessor agency.
It is one of the most effective orally administered opioid analgesics and has a wide safety margin. While codeine can be directly extracted from opium, its original source, most codeine is synthesized from the much more abundant morphine through the process of O- methylation  through a process first completed in the late 20th century by Robert C. Corcoran and Junning Ma.
They quickly succeeded using petroleum or coal tar and a process developed at the United States' National Institutes of Health. Numerous codeine salts have been prepared since the drug was discovered. The most commonly used are the hydrochloride freebase conversion ratio 0. The latter was introduced as Codeonal inindicated for pain with nervousness. Codeine hydrochloride is more common worldwide and the citrate, hydroiodide, hydrobromide, tartrate, and other salts are also seen.
Brand named as Phenergan with Codeine or in generic form as promethazine with codeine. In the s it started to be mixed with soft drinks to be used as a recreational drug and was called 'syrup', 'lean', or ' purple drank '. Drug abuse screening programs generally test urinehairsweat or saliva.
Many commercial opiate screening tests directed at morphine cross-react appreciably with codeine and its metabolites, but chromatographic techniques can easily distinguish codeine from other opiates and opioids.
It is important to note that codeine usage results in significant amounts of morphine as an excretion product. Furthermore, heroin contains codeine or acetyl codeine as an impurity and its use will result in excretion of small amounts of codeine. Poppy seed foods represent yet another source of low levels of codeine in one's biofluids.
Codeine - Wikipedia
Australia[ edit ] In Australia, Since February 1,preparations containing codeine are not available without a prescription. Schedule 8 preparations are subject to the strictest regulation of all medications available to consumers. A similar tablet called "A. Both tablets are kept behind the counter and must be dispensed by a pharmacist who may limit quantities.
Names of many codeine and dihydrocodeine products in Canada tend to follow the narcotic content number system Tylenol With Codeine No.
Codeine became a prescription-only medication in the province of Manitoba on February 1, A pharmacist may issue a prescription, and all purchases are logged to a central database to prevent overprescribing.
In Austriathe drug is listed under the Suchtmittelgesetz in categories corresponding to their classification under the Single Convention on Narcotic Drugs.
Therefore, the detection of morphine alone does not provide complete information about the source of the compound. Moreover, dietary poppy seeds contain some codeine and morphine, and their ingestion may produce a positive urine test for opiates.
The amounts of urinary codeine and morphine after poppy seed ingestion have been summarized in a review article 1. Initial screening tests by radioimmunoassay followed by gas chromatography GC 1 confirmatory tests were introduced by the Department of Defense DoD in for monitoring the use of controlled substances by military personnel.
Specimens found positive in the screening test were tested by a GC confirmation procedure for codeine and morphine. In confirmation, total conjugated and unconjugated codeine and total morphine were tested after acid hydrolysis of the corresponding conjugated compounds. Inthe GC confirmation procedure was replaced by a more reliable gas chromatography—mass spectrometry GC-MS confirmation procedure 2.
Almost immediately, all opiate-positive specimens were reported with a caution that explained the effect of poppy seed on test results. InDoD introduced detection of 6-acetylmorphine 6-AMa unique metabolite of heroin, as a tool to confirm heroin use 3.
As part of the protocol, all results were required to be reviewed by a Medical Review Officer to ensure that the positive results were not because of legitimate use of codeine and morphine or by ingestion of dietary poppy seeds. The Medical Review Officer examined donors for evidence of drug abuse by taking a clinical history and performing a physical examination, and often requested a test for 6-AM to confirm heroin use.
In the guidelines, no cutoff was mandated for 6-AM confirmation. Generally, the limit of detection LOD of a procedure was used to confirm the presence of 6-AM in urine. Because the LOD varied considerably between laboratories, the 6-AM results were misleading in some forensic investigations.
Later in a separate memorandum, the DHHS postponed the implementation date until December 1,because additional time was needed to validate immunoassay test kits and 6-AM confirmatory procedures.
Because 6-AM is a unique metabolite of heroin, its presence in urine would be used to confirm heroin use. The objective of the new cutoff concentrations was to eliminate a considerable number of specimens that may be positive from poppy seed use. The objective of this study was to determine appropriate cutoff concentrations for free codeine, free morphine, and 6-AM that could be substituted for the cutoff concentrations for total morphine, total codeine, and 6-AM, using retrospective published data 7 8 9and to develop a confirmatory assay that would allow simultaneous measurement of free morphine, free codeine, and 6-AM.
The combined objective was to propose a method for identifying codeine, morphine, and heroin use with one urine immunoassay and one confirmation test. Materials and Methods chemicals, reagents, and supplies Codeine and morphine were purchased from Sigma Chemical Co. Propionic anhydride and pentafluoropropionic anhydride were purchased from Aldrich Chemical Co. The MSD was operated under electron impact mode.
The ion window and dwell time were 0. The electron multiplier was set at the autotune voltage for codeine and morphine, and V above autotune for 6-AM. The flow rate of helium through a DB-5MS capillary column [5: In brief, the samples for morphine analysis were hydrolyzed with acid.
After an acid-base separation, the morphine was extracted by solvent and then detected by GC-MS as acetyl derivative. Acid hydrolysis was avoided for 6-AM analysis.
The compound was extracted using a procedure similar to morphine and was detected as the propionyl derivative. All positive samples were quantified, allowing a retrospective application of different cutoffs for study purposes. For extraction, a mixture of internal standards, d6-codeine, d3-morphine, and d6-AM 15, 15, and 0. A negative control was used to verify contamination during analysis.