Codeine, determination

Greenway, G.M., Nelstrop, L.J., Port, S.N., Tris(2,2-bipyridyl)ruthenium (II) chemiluminescence in a microflow injection system for codeine determination. Anal. Chim. Acta 2000, 405(1-2), 43-50. 

Barnett and colleagues developed a new method for determining the concentration of codeine during its extraction from poppy plants. As part of their study they determined the method s response to codeine relative to that for several potential interferents. For example, the authors found that the method s signal for 6-methoxycodeine was 6 (arbitrary units) when that for an equimolar solution of codeine was 40. 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

Figure 11.12 GC analysis of (a) urine sample spiked with opiates 3 p.g/ml) and (b) blank urine sample. Peak identification is as follows 1, dihydrocodeine 2, codeine 3, ethylmor-phine 4, moipliine 5, heroin. Reprinted from Journal of Chromatography, A 771, T. Hyotylainen et al., Determination of morphine and its analogues in urine by on-line coupled reversed-phase liquied cliromatography-gas clrromatography with on-line derivatization, pp. 360-365, copyright 1997, with permission from Elsevier Science.

This experiment33 illustrates how adjustment of pH may be used to control fluorescence and so make the determination more specific. The alkaloids codeine and morphine can be determined independently because whilst both fluoresce strongly at the same wavelength in dilute sulphuric acid solution, morphine gives a generally negligible fluorescence in dilute sodium hydroxide. The fluorescence intensities of the two compounds are assumed to be additive. 

Sflf-Tfst 8.12A Use the data in Table 8.8 to determine at what temperature a 0.20 mol-kg 1 solution of the analgesic codeine, C18H21NO , in benzene will freeze. 

Typical examples that fall in this group would be the determination of the active ingredients in analgesic tablets for pharmaceutical use, such as aspirin or codeine or the analysis of a food product such as margarine. Examples of both these analyses will be described to illustrate the sample preparation procedure. 

Codeine phosphate was duly extracted into CS2 and quantitatively determined by measuring its absorption at 942 cm1. 

The presence of foreign alkaloids in Codeine (BP) may be determined by more or less an identical method as already discussed in section 28.4.3 earlier. 

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. 

Lee H-M, Lee C-W. 1991. Determination of morphine and codeine in blood and bile by gas chromatography with a derivatization procedure. J Anal Toxicol 15 182. 

He H, Shay SD, Caraco Y, Wood M, Wood AJ. 1998. Simultaneous determination of codeine and its seven metabolites in plasma and urine by high-performance liquid chromatography with ultraviolet and electrochemical detection. J Chromatogr B Biomed Sci Appl 708(1-2) 185-193. 

Bogusz MJ, Maier RD, Erkens M, Driessen S. 1997. Determination of morphine and its 3- and 6-glucuronides, codeine, codeine-glucuronide and 6-monoacetylmorphine in body fluids by liquid chromatography atmospheric pressure chemical ionization mass spectrometry. J Chromatogr B Biomed Sci Appl 703 115. 

An MEKC method for the determination of ibuprofen, codeine phosphate hemihydrate, their nine potential degradation products, and impurities in a commercial tablet formulation was developed, optimized, and fully validated according to ICH guidelines and submitted to the regulatory authorities. The optimized system containing ACN as organic modifier allowed baseline separation of ibuprofen, codeine, and nine related substances within 12 min. 

The initial metabolism of heroin involves loss of one acetyl group, forming6-monoacetylmorphine, or 6-MAM. If6-MAM is detected in body fluids and tissues, it can only have come from heroin. When 6-MAM is further metabolized, it loses the second acetyl group and forms morphine. At this point, finding morphine, is not helpful in determining whether the individual had used heroin or morphine, or even codeine, since it also is metabolized to morphine. 

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