Analysis of “Morphine base”

Morphine base is a crude preparation of alkaloids obtained from opium by the lime method and mainly used in the illicit manufacture of heroin. It has recently been found to be abused as a narcotic in itself and administered by intravenous injection. Analysis by thin layer chromatography, gas chromatography, and gas chromatography — mass spectrometry has shown it to contain morphine as the predominant alkaloid but in addition small amounts of codeine, narcotine, thebaine, papaverine and cryptopine. Morphine has been detected in the urine of people who have abused the drug.     

Induction of physical dependence in rats by short interval medication

Rats were intermittently medicated at one hour intervals through an implanted intravenous cannula. Physical dependence on morphine and codeine was developed rapidly and it was detectable with the maintenance dose as low as 9.6 mg/kg/day. Physical dependence on pentazocine was also developed with the maintenance dose of 96 mg/kg/day, but was not with 9.6 mg/kg/day. In the pentazocine-treated rats, body weight loss was observed after the abrupt withdrawal, and abstinence signs were precipitated by naloxone 1 mg/kg. Cross physical dependence between morphine and pentazocine was demonstrated. Pentazocine suppressed the abstinence signs of rats weakly dependent on morphine, and morphine suppressed those of pentazocine-dependent rats. ID-1229, a new benzomorphan analgesic, did not produce dependence in this test and did not suppress the abstinence signs of morphine- and pentazocine-dependent rats.     

HPLC and GC-MS screening of Chinese proprietary medicine for undeclared therapeutic substances

Traditional Chinese medicine includes raw medicinal materials and Chinese proprietary medicine (CPM). Despite being of natural origin, toxic effects, adulteration with synthetic therapeutic substances and even deaths had been associated with CPM. There is thus a need to develop analytical technique to rapidly screen for undeclared toxic and therapeutic substances in CPM. In this study, a high performance liquid chromatography-diode-array detection method was developed and used to screen for undeclared therapeutic substances in CPM. An ultraviolet (UV) library of 266 drugs had been compiled. Solute identification was performed by comparing the analytical data (UV spectra, retention time and relative retention time) with those of the 266 standards. Gas chromatography-mass spectrometry was used as a confirmation method. These chromatographic methods had been shown to be selective and reproducible in screening for undeclared drugs in CPM. Using the method developed, 41 CPM samples in seven categories were screened for undeclared therapeutic substances. One anti-asthmatic CPM was found to contain codeine.     

Lack of impairment due to confirmed codeine use prior to a motor vehicle accident: Role of pharmacogenomics

BackgroundWe examined forensic serum toxicology and pharmacogenomics data from a woman on codeine shortly before she caused a motor vehicle accident.MethodsA woman driving erratically collided with a parked car of a highway seriously injuring 2 men working to repair the parked vehicle. The woman tested positive for codeine, acetaminophen and barbital. She had been taking these medications for 20 years due to migraine headache. Serum toxicology and genotype analysis for cytochrome P450, UDP glucuronosyltransferase, and other metabolizing enzymes were measured.ResultsThe woman was tried and convicted of driving under the influence resulting in bodily harm and was sentenced to 6 years. Toxicology results on peripheral blood showed a total and free codeine of 840 and 348 μg/L, respectively, and total morphine of 20 μg/L (17, 3, and 0 μg/L for morphine-3-glucuronide, morphine-6-glucuronide, and free morphine, respectively). She was heterozygous for CYP 2D6 *2/*4 (extensive/poor metabolism) and heterozygous for UGT 2B7 *1/*2 (extensive/ultra-rapid metabolism). The woman was also taking fluoxetine and bupropion which are strong inhibitors of CYP 2D6.ConclusionsBased on her genotype and phenotype and reports by the arresting officer, we suggest that the subject in question was not intoxicated by opiates at the time of her motor vehicle accident and may have been falsely incarcerated.     

酒石酸双氢可待因与磷酸可待因治疗癌痛的双盲随机对照研究

目的：比较酒石酸双氢可待因和磷酸可待因治疗中度癌痛的疗效和不良反应。方法：采用随机双盲对照研究，对69例有中度癌痛的肿瘤患者用酒石酸双氢可待因和磷酸可待因进行治疗，观察疗效和不良反应．结果：双氢可待因与磷酸可待因用于中度癌痛患者，两者在镇痛强度上无显著差异，不良反应与其他阿片类药物类似．结论：酒石酸双氢可待因和磷酸可待因可用于治疗中度癌痛。     

Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake

Objective: The analgesic effect of codeine depends on its O-demethylation to morphine via sparteine oxygenase (CYP2D6) in the liver and presumably also via this enzyme in the CNS. We studied the ability of quinidine, which is a potent inhibitor of CYP2D6, to penetrate the blood brain barrier and its pssible impact on codeine O-demethylation in CNS. Methods: The study comprised 16 extensive and one poor metaboliser of sparteine, who underwent spinal anaesthesia for urinary tract surgery or examination. Eight patients were given an oral dose of 125 mg codeine and 9 patients (including the poor metaboliser) were given 200 mg quinidine 2 h before the same dose of codeine. Plasma and spinal fluid samples were collected 2 h after codeine intake. Results: Free concentrations of quinidine were 11-times lower in cerebrospinal fluid than in plasma, and ranged from 9–15 nmol·l^–1. Morphine concentrations were significantly lower in patients pre-treated with quinidine, both in plasma (median 1.45 nmol·l^–1, range 0.74–1.95 nmol·l^–1 vs 9.86 nmol·l^–1, range 4.59–28.4 nmol·l^–1) and in cerebrospinal fluid (0.23, 0.16–0.61 nmol·l^–1 vs 3.63, 0.6–8.09 nmol·l^–1). The morphine/codeine concentration ratio in plasma (3.07×10^–3, 1.68–3.68×10^–3 vs 19.87×10^–3, 9.87–66.22×10^–3) and in cerebrospinal fluid (0.83×10^–3, 0.58–1.45×10^–3 vs 7.19×10^–3, 2.03–17.7×10^–3) was also lower. The morphine/-codeine concentration ratios were significantly lower in cerebrospinal fluid both without and with quinidine, but the difference between the plasma and spinal fluid ratios was significantly smaller with quinidine than without (p=0.0002). Conclusion: Quinidine penetrates the blood brain barrier poorly, but quinidine pre-treatment leads to pronounced lowering of the cerebrospinal fluid concentration of morphine after codeine intake. However, the O-demethylation of codeine in CNS may not be totally blocked by quinidine.     

双波长薄层扫描法对磷酸可待因氧化降解动力学的研究

本文采用双波长薄层扫描法研究了镇痛药氨酚待因片中磷酸可待因的稳定性。测得磷酸可待因在不同温度下的氧化降解速度常数k与氧化降解反应活化能E,并求出氨酚待因片在常温(25℃)下的贮存期t_(0.9),以及磷酸可待因氧化降解产物随时间的变化规律。     

The effect of codeine on gastrointestinal transit in extensive and poor metabolisers of debrisoquine

Methods: Codeine (50 mg) was administered to 12 extensive metabolisers (EM) and 12 poor metabolisers (PM) of debrisoquine. The oro-caecal transit time was estimated by the hydrogen breath test. The urinary excretion of codeine and metabolites during a 6-h interval was estimated after simultaneous analysis of codeine, morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), morphine (M), normorphine (NM), norcodeine, norcodeine glucuronide and codeine-6-glucuronide using HPLC. Results: The mean transit times after placebo were 1.3 h in the EM and 1.4 h in the PM. The corresponding figures after ingestion of codeine were 2.2 h and 2.1 h. The differences between the groups were statistically and clinically insignificant. The effect of codeine compared with placebo was significantly different in both groups. As expected, the metabolites of the O-demethylation pathway, M, M6G, M3G and NM were significantly lower in the PM. Interestingly, the recovery of the dose in the form of codeine (>1.7 times) and norcodeine (>2.5 times) was significantly higher in the PM, indicating compensatory metabolism via N-demethylation. Conclusion: In contrast to the analgesic effect, the prolongation of gastrointestinal transit caused by the drug does not depend on the formation of O-demethylated active metabolites M, M6G or NM. Received: 15 November 1996 / Accepted in revised form: 10 April 1997     

曲马多止咳作用的临床观察

目的 :观察曲马多对剧烈干咳患者的止咳效果。方法 :将98例剧烈干咳或干咳伴有胸痛的患者分为3组 ,分别给予曲马多胶囊、磷酸可待因和复方甘草片 ,给药后观察各药止咳效果及其对胸痛的影响。结果 :曲马多可以缓解病人的剧烈干咳 ,其止咳疗效显著强于复方甘草片 (P<0.01)与磷酸可待因相似 (P>0.05) ,曲马多和可待因缓解胸痛的作用明显优于复方甘草片(P<0.05)。结论 :曲马多对剧烈干咳以及干咳伴胸痛患者具有显著的止咳和镇痛作用