Quantitative analysis codeine

Newer methods of chemical analysis led to the isolation of the major alkaloids from crude drug preparations. By 1833, aconitine, atropine, codeine, hyoscyamine, morphine, nicotine, and strychnine had been isolated from plants. Color tests for alkaloids were developed between 1861 and 1882 by 1890 quantitative analysis methods became available. Physiological tests for alkaloids, particularly strychnine, first used in 1856, were employed well into the twentieth century. Tests for alcohol, devised by Lieben (iodoform crystal test, 1870) and others, were later perfected for the quantitative analysis of alcohol in body fluids and tissues. Qualitative tests for carbon monoxide in the blood were developed about this time and in 1880, Fodor developed a palladium chloride reduction method to quantitate carbon monoxide in blood. 

Gough and Baker studied a number of conventional and modified stationary phases in order to find the best one for quantitative gas chromatography of heroin and structurally related compounds. Silanized 0V-210 was found to be the most suitable for the separation of heroin, codeine, acetylcodeine, morphine and 6-0-monoacetylmorphine. It gave the best reproducibility of retention times and less losses of the compounds by adsorption. For quantitative analysis 2.8 m by 4 mm I.D. glass columns and Diatomite CLQ, 80-100 mesh, as solid support were used at a column temperature of 225°C. Despite the fact that some of the compounds, particularly morphine, suffered adsorption losses during gas chromatography, these losses were reproducible, and satisfactory quantitative data could be obtained, as shown in Table 14.19. 

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]. 

Klein applied gas chromatography. 3-0-acetylmorphine results from an incomplete esterification of morphine with acetic anhydride and the amount may be of value for forensic purposes. Because of the very small amounts present in heroin, the compound was derivatized with hepta-fluorobutyric anhydride and gas chromatographed with a Ni electron capture detector on a 3 1 OV-17 on Gas Chrom Q packed column at 230°C using chlorpromazine as an internal standard. The heptafluorobutyric anhydride derivatives were extracted quantitatively from the reaction mixture with light petroleum and were stable for several hours in this solvent. However, it was recommended that upon formation, the analysis should be completed without delay. The analysis was carried out with 1-10 mg heroin samples and the amount of 3-0-acetylmorphine varied from 0.1 to 2 %, acetylcodeine from 3 to 15, morphine and codeine from 0.01 to 0.5. ... 

Van Vendeloo et al. developed a gas chromatographic method for fingerprint analysis of illicit heroin samples, capable of detecting the main components acetyl codeine, caffeine, codeine, heroin, 6-0-monoacetylmorphine, morphine and quinine in one run in 25 min. Heroin, morphine, codeine and caffeine could be quantified directly, 6-0-monoacetylmorphine and acetylcodeine were not fully separated. Quantitation of the latter two required acetylation of 6-0-monoacetylmorphine to heroin. A packed column of 1 % OV-1 on Chromosorb G HP was used... 

Capillary gas chromatography of morphine and codeine was described by Christophersen and Rasmussen in connection with their studies on flash heater derivatization of drugs for gas chromatographic analysis. Derivatization was found necessary for relative polar compounds such as morphine and codeine because of the often undesirable adsorption observed with glass capillary columns. Trimethylsilylation was performed with N,0-bis-(trimethylsilyl)acetamide and ethylmorphine was used as an internal standard for the quantitative determinations on a 20 m by 0.35 mm I.D. glass capillary, wall coated with SE-30. Calibration graphs for concentrations of 1-10 yg/ml in ethylacetate were constructed. The data obtained from the reproducibility test showed that at 5.0 pg/ml the relative standard deviation was 1.5 % for codeine and 4.3 % for morphine. 

Because of adsorption and degradation problems when using glass capillary columns for the analysis of morphine and codeine, Plotczyk preferred fused silica columns to the analysis of underivatized drugs, i.a. codeine. He used cold on-column injection and cross-linked poly-si loxane deactivated columns and obtained linear quantitation from 1 to 100 ng with precisions of 0.1-2 % for some of the drugs analyzed. 

Lurie, I.S. McGuiness, K. The quantitation of heroin and selected basic impur-ties via reversed phase HPLC. II. The analysis of adulterated samples. J.Liq.Chromatogr., 1987, 10, 2189—2204 [also impurities, acetaminophen, acetylcodeine, acetylmorphine, acetylprocaine, aminopyrene, amitriptyline, antipyrene, aspirin, barbital, benztropine, caffeine, cocaine, codeine, diamorphine, diazepam, diphenhydramine, dipyrone, ephedrine, ethylmorphine, lidocaine, meconin, methamphetamine, meth-ap Tilene, methaqualone, monoacetylmorphine, morphine, nalorphine, niacinamide, nicotinamide, noscapine, papaverine, phenacetin, phenmetrazine, phenobarbital, phenolphthalein, procaine, pro-panophenone, propoxyphene, P5rilamine, quinidine, quinine, salic lamide, saUsalicylic acid, secobarbital, strychnine, tetracaine, thebaine, tripelennamine, tropacocaine, vitamin B3, vitamin B5 electrochemical detection]... 

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