Heroin can be metabolized easily in body and the mail metabolites are 6-MAM, morphine and so on. At present, there are urine, blood, hair and so on as specimens for detection, while the analytical technology conclude TLC, GC, HPLC, GC/MS, LC/MS, IA, CE etc. In this paper, these technologies used for heroin's metabolites were viewed in order to provide some reference to the study in relative field.
Chromatography, High Pressure Liquid ; Forensic Medicine ; Gas Chromatography-Mass Spectrometry ; Hair/chemistry* ; Heroin/metabolism* ; Heroin Dependence/metabolism* ; Humans ; Morphine/analysis* ; Morphine Derivatives/analysis* ; Substance Abuse Detection/methods*

The paper reports the establishment of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous analysis of 11 opiates in hair samples, and the study of presence of opiates in the hair of active heroin addicts. About 20 mg of decontaminated and pulverized hair sample was hydrolyzed with buffer solution for 30 min, in the presence of morphine-d3 and acetylmorphine-d6 used as internal standards, and then extracted with the mixture of dichlormethane and isopropanol, separated by the Allure PFP propyl column with a mobile phase consisting of acetonitrile and 20 mmol L(-1) ammonium acetate buffer, and then analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was used to analyze 11 opiates. Eleven opiates showed a fairly good linearity over the corresponding range (r > 0.996 0). The detection limits were less than 0.05 ng mg(-1). The recoveries were between 47.2% and 110%, and the deviations of intra- and inter-day precision were less than 14%. Heroin, acetylmorphine, morphine, codeine, acetylcodeine and hydrocodone were detected in hair samples of 21 herion addicts. The developed method shows high sensitivity and selectivity, and is suitable for the simultaneous analysis of 11 opiates in hair samples and identify legal and illegal use of opiates.
Analgesics, Opioid ; analysis ; Chromatography, Liquid ; methods ; Codeine ; analogs & derivatives ; analysis ; Hair ; chemistry ; Heroin ; analysis ; Humans ; Hydrocodone ; analysis ; Limit of Detection ; Morphine ; analysis ; Morphine Derivatives ; analysis ; Sensitivity and Specificity ; Substance Abuse Detection ; methods ; Tandem Mass Spectrometry ; methods

The purpose of the present study is to analyze the relationship between the telemetry electroencephalogram (EEG) changes of the prelimbic (PL) cortex and the drug-seeking behavior of morphine-induced conditioned place preference (CPP) rats by using the wavelet packet extraction and entropy measurement. The recording electrode was stereotactically implanted into the PL cortex of rats. The animals were then divided randomly into operation-only control and morphine-induced CPP groups, respectively. A CPP video system in combination with an EEG wireless telemetry device was used for recording EEG of PL cortex when the rats shuttled between black-white or white-black chambers. The telemetry recorded EEGs were analyzed by wavelet packet extraction, Welch power spectrum estimate, normalized amplitude and Shannon entropy algorithm. The results showed that, compared with operation-only control group, the left PL cortex's EEG of morphine-induced CPP group during black-white chamber shuttling exhibited the following changes: (1) the amplitude of average EEG for each frequency bands extracted by wavelet packet was reduced; (2) the Welch power intensity was increased significantly in 10-50 Hz EEG band (P < 0.01 or P < 0.05); (3) Shannon entropy was increased in β, γ₁, and γ₂waves of the EEG (P < 0.01 or P < 0.05); and (4) the average information entropy was reduced (P < 0.01). The results suggest that above mentioned EEG changes in morphine-induced CPP group rat may be related to animals' drug-seeking motivation and behavior launching.
Animals ; Conditioning (Psychology) ; Drug-Seeking Behavior ; Electroencephalography ; Entropy ; Morphine ; pharmacology ; Prefrontal Cortex ; drug effects ; Rats ; Telemetry ; Wavelet Analysis

The paper is to establish a method for simultaneous determination of 5 kinds of alkaloids in ephedra and poppy which are in Kechuanning tablets. Solid-phase extraction (SPE) was adopted in pretreatment, and a UPLC method with 2 different wavelengths had been developed: 210 nm for the detection of morphine, codeine phosphate, ephedrine hydrochloride and pseudoephedrine hydrochloride, and 251 nm for papaverine hydrochloride. The column used was Acquity UPLC BEH C18 (100 mm x 2.1 mm ID, 1.7 microm) with linear gradient elution using acetonitrile and 0.1% phosphoric acid. The flow rate was 0.4 mL.min-1, and the column temperature was 30 degrees C. The linear response range was 0.375 0 - 12.50 microg.mL-1 for morphine, 0.064 32 - 2.144 microg.mL-1 for codeine phosphate, 0.030 06 - 1.002 microg.mL-1 for papaverine hydrochloride, 1.126 - 37.52 microg.mL-1 for ephedrine hydrochloride, 0.287 8 - 9.592 microg.mL-1 for pseudoephedrine hydrochloride (r = 0.999 7). The average recoveries of these compounds were 99.26%, 100.6%, 95.29%, 100.1% and 97.48%, respectively. This is a more reasonable and credible method of quality control for Kechuanning tablets.
Alkaloids ; analysis ; Chromatography, High Pressure Liquid ; Codeine ; analysis ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Ephedra ; chemistry ; Ephedrine ; analysis ; Morphine ; analysis ; Papaver ; chemistry ; Papaverine ; analysis ; Plants, Medicinal ; chemistry ; Pseudoephedrine ; analysis ; Quality Control ; Solid Phase Extraction ; Tablets

BACKGROUNDOpioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown. The µ-opioid receptor (MOR) has an important role in mediating the actions of morphine and other analgesic agents. This study is aimed at exploring the changes of MOR in the periaqueductal gray (PAG) in rats when morphine is substituted for equianalgesic fentanyl.

METHODSForty rats were randomly assigned to five treatment groups: 7 days normal saline group (N group), 7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM group). Rats repeatedly received subcutaneous injections of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats' antinociceptive response to thermal pain was evaluated by the tail flick latency assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.

RESULTSThis study showed that after morphine was substituted with fentanyl on day 8, the tail flick latency (TFL) increased from (3.9 ± 0.4) seconds to (11.4 ± 0.4) seconds. The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group (P < 0.05) but more than that in MM group (P < 0.05).

CONCLUSIONSEquianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance, which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.

Analgesics, Opioid ; pharmacology ; Animals ; Drug Tolerance ; Fentanyl ; pharmacology ; Male ; Morphine ; pharmacology ; Periaqueductal Gray ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; analysis ; genetics

OBJECTIVE: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of opiates in biological samples according to the emerging problem in drugs abuse. METHODS: Opiates such as heroin, 6-acetylmorphine, morphine, codeine, acetylcodeine, hydrocodone and hydromorphone were isolated from human blood, urine, oral fluid and hair using a simple extraction and consequently analyzed using LC-MS/MS. The method was evaluated by real cases. RESULTS: The mobile phase give the optimum separation for opiates. The detection limit of morphine in urine with dilution and liquid-liquid extraction and in hair is 10ng/mL, 0.01 ng/mL and 0.01 ng/mg, respectively. CONCLUSION The method is simple and rapid, offering superior sensitivity and selectivity for opiates. The target compounds comprising hydrocodone and hydromorphone enlarge the applied area.
Chromatography, Liquid ; Codeine/analysis* ; Forensic Medicine/methods* ; Hair/chemistry* ; Humans ; Hydrocodone/analysis* ; Hydromorphone/analysis* ; Morphine/analysis* ; Narcotics/analysis* ; Reproducibility of Results ; Saliva/chemistry* ; Substance Abuse Detection/methods* ; Tandem Mass Spectrometry

Adult ; Analgesics, Opioid ; pharmacology ; Female ; Fentanyl ; pharmacology ; Humans ; In Vitro Techniques ; Interleukin-6 ; blood ; Male ; Morphine ; pharmacology ; Narcotics ; pharmacology ; Tumor Necrosis Factor-alpha ; analysis

Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.
Administration, Intranasal ; Amylases ; Analgesics, Opioid ; Blood Gas Analysis ; Emergencies ; Humans ; Lipase ; Miosis ; Morphine ; Naloxone ; Naltrexone ; Nausea ; Pancreas ; Physical Examination ; Porphyrins ; Pruritus ; Pupil ; Reference Values ; Respiration ; Respiratory Insufficiency

BACKGROUND: The aim of this study was to evaluate the effects of respiratory depression of IV-PCA using morphine which has potent respiratory depression or nalbuphine which has less potent respiratory depression among opioids. METHODS: Forty patients were divided into two groups; Group M was used morphine, and Group N was used nalbuphine as a drug for IV-PCA. When patient emerges from general anesthesia, Group M was given initial bolus of 0.1 ml/kg of 0.1% morphine solution and connected Basal Bolus PCA infusor R containing morphine 50 mg per 40 ml in normal saline. Group N, similarly Group M, was given initial bolus of 0.1 ml/kg of 0.1% nalbuphine solution, and connected PCA infusor containing nalbuphine 50 mg per 40 ml in normal saline. To compare respiratory depression, arterial blood gas analyses were done preoperatively and at 1, 6 and 12 hour after IV-PCA. Simultaneously, analgesic and side effects were evaluated. RESULTS: There were no remarkable respiratory depression such as hypercarbia(PaCO2 > 50 mmHg), hypoxemia(PaO2 < 60 mmHg) and slow respiratory rate in both groups. Analgesic and side effects were similar in both groups. CONCLUSIONS: We conclude that IV-PCA using morphine or nalbuphine is relatively effective and safe method for the postoperative pain control. Ordinarily, IV-PCA dose not induce respiratory depression unless overdose in careless or mistaken mishaps are developed.
Analgesia, Patient-Controlled* ; Analgesics, Opioid ; Anesthesia, General ; Blood Gas Analysis ; Humans ; Infusion Pumps ; Morphine* ; Nalbuphine* ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Respiratory Insufficiency* ; Respiratory Rate

BACKGROUND: While the combination therapy of morphine and benzodiazepine has been recommended as a standard therapy for sedation and analgesia in patients with mechanical ventilation, morphine can suppress respiratory center, and also decrease blood pressure and bowel movement. Because ketamine has analgesic and sedative effects compatible to morphine without depression of the cardiovascular and respiratory systems in addition to the preservation of bowel activity, ketamine may substitute morphine. However, it has not well known such potential advantages of ketamine in patients with mechanical ventilation. METHODS: Thirty eight patients (male:female=30:8, age=62.6 +/- 11.7 years) with mechanical ventilation were randomized as ketamine and morphine group (n=21 vs. n=17). There was no significant differences in sex, age and APACHE III score at the initiation of mechanical ventilation (ketamine group, morphine group: 79.4 +/- 2.0, 82.0 +/- 20.6). The study duration was 24 h after drug administration and minimum dose, which maintains ventilator-patient synchrony or the status of Ramsay score 3, was used. Ramsay sedation score, hemodynamic variables, respiratory and arterial blood gas variables, and bowel sound were measured at every 4 h. Arterial blood gas analysis was checked at 0, 4, and 24 h. RESULTS: 1) There were no significant differences in Ramsay sedation score and other hemodynamic, respiratory, and arterial blood gas variables in each group. The dose of combined midazolam was not different between two groups (ketamine vs. morphine; 52.1 +/- 11.9 vs. 46.7 +/- 15.1 mg/d; p=0.23). 2) The cases with decreased mean arterial pressure over 25% of the baseline shortly after the drug administration less frequently observed in ketamine group, although the difference did not reach statistical significance (n=2, 9.5% vs. n=5, 29.4%; p=0.12). 3) Bowel movement reduction at 4 h after the drug administration was less in ketamine group (n=1, 4.8% vs. n=6, 35.3%, p=0.03). The difference was not observed at 8 h. 4) Cost of the drug for 24 h was more expensive in ketamine group (dose & cost; 688 506 mg/d & 25,891 7,743 won vs. 40 +/- 18 mg/d, 15,814 +/- 4,853 won; p<0.001). CONCLUSIONS: Considering the advantages in the hemodynamics and bowel movement, ketamine may substitute morphine for the sedation of patients with mechanical ventilation, if indicated.
Analgesia* ; APACHE ; Arterial Pressure ; Benzodiazepines ; Blood Gas Analysis ; Blood Pressure ; Depression ; Hemodynamics ; Humans ; Hypnotics and Sedatives ; Ketamine* ; Midazolam ; Morphine* ; Respiration, Artificial* ; Respiratory Center ; Respiratory System