GC-MS confirmation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in urine.
A procedure for the simultaneous confirmation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in urine specimens by gas chromatography-mass spectrometry (GC-MS) is described. After the addition of nalorphine and naltrexone as the two internal standards, the urine is hydrolyzed overnight with beta-glucuronidase from E. coli. The urine is adjusted to pH 9 and extracted with 8% trifluoroethanol in methylene dichloride. After evaporating the organic, the residue is sequentially derivatized with 2% methoxyamine in pyridine, then with propionic anhydride. The ketone groups on hydrocodone, hydromorphone, oxycodone, oxymorphone, and naltrexone are converted to their respective methoximes. Available hydroxyl groups on the O3 and O6 positions are converted to propionic esters. After a brief purification step, the extracts are analyzed by GC-MS using full scan electron impact ionization. Nalorphine is used as the internal standard for codeine, morphine, and 6-acetylmorphine; naltrexone is used as the internal standard for the 6-keto-opioids. The method is linear to 2000 ng/mL for the 6-keto-opioids and to 5000 ng/mL for the others. The limit of quantitation is 25 ng/mL in hydrolyzed urine. Day-to-day precision at 300 and 1500 ng/mL ranged between 6 and 10.9%. The coefficients of variation for 6-acetylmorphine were 12% at both 30 and 150 ng/mL. A list of 38 other basic drugs or metabolites detected by this method is tabulated. (+info)
Incomplete, asymmetric, and route-dependent cross-tolerance between oxycodone and morphine in the Dark Agouti rat.
Our previous studies indicate that oxycodone is a putative kappa-opioid agonist, whereas morphine is a well documented micro-opioid agonist. Because there is limited information regarding the development of tolerance to oxycodone, this study was designed to 1) document the development of tolerance to the antinociceptive effects of chronically infused i.v. oxycodone relative to that for i. v. morphine and 2) quantify the degree of antinociceptive cross-tolerance between morphine and oxycodone in adult male Dark Agouti (DA) rats. Antinociceptive testing was performed using the tail-flick latency test. Complete antinociceptive tolerance was achieved in 48 to 84 h after chronic infusion of equi-antinociceptive doses of i.v. oxycodone (2.5 mg/24 h and 5 mg/24 h) and i.v. morphine (10 mg/24 h and 20 mg/24 h, respectively). Dose-response curves for bolus doses of i.v. and i.c.v. morphine and oxycodone were produced in naive, morphine-tolerant, and oxycodone-tolerant rats. Consistent with our previous findings that oxycodone and morphine produce their intrinsic antinociceptive effects through distinctly different opioid receptor populations, there was no discernible cross-tolerance when i.c.v. oxycodone was given to morphine-tolerant rats. Similarly, only a low degree of cross-tolerance (approximately 24%) was observed after i.v. oxycodone administration to morphine-tolerant rats. By contrast, both i.v. and i.c.v. morphine showed a high degree of cross-tolerance (approximately 71% and approximately 54%, respectively) in rats rendered tolerant to oxycodone. Taken together, these findings suggest that, after parenteral but not supraspinal administration, oxycodone is metabolized to a mu-opioid agonist metabolite, thereby explaining asymmetric and incomplete cross-tolerance between oxycodone and morphine. (+info)
An unusual multiple drug intoxication case involving citalopram.
A 47-year-old male with a history of drug abuse and suicide attempts was found dead at home. The death scene investigation showed evidence of cocaine abuse and multiple drug ingestion. Citralopram, a new selective serotonin reuptake inhibitor, cocaine, oxycodone, promethazine, propoxyphene, and norpropoxyphene were identified and quantitated in the postmortem samples by gas chromatography-mass spectrometry. The concentration of citalopram in the femoral blood was 0.88 mg/L. The heart blood concentration was 1.16 mg/L. Femoral blood concentrations of the other drugs were as follows: cocaine, 0.03 mg/L; oxycodone, 0.06 mg/L; promethazine, 0.02 mg/L; propoxyphene, 0.02 mg/L; and norpropoxyphene, 0.07 mg/L. Other tissue samples were also analyzed. The concentrations of cocaine, oxycodone, promethazine, and propoxyphene in the blood, liver, brain, and gastric contents did not suggest an intentional overdose. However, the possibility of multiple drug interactions including citalopram was evident. In this case, the citalopram concentrations were consistent with those reported in fatal cases involving multiple drug use. Citalopram was present in urine at a concentration of 0.9 mg/L. (+info)
Kinetics and inhibition of the formation of 6beta-naltrexol from naltrexone in human liver cytosol.
AIMS: To determine the kinetics of the formation of 6beta-naltrexol from naltrexone in human liver cytosol, and to investigate the role of potential inhibitors. METHODS: The kinetics of the formation of 6 beta-naltrexol from naltrexone were examined in eight human liver cytosol preparations using h.p.l.c. to quantify 6 beta-naltrexol and, the extent of inhibition of 6 beta-naltrexol formation was determined using chemical inhibitors. The formation of 6 beta-naltrexol and the back reaction of 6 beta-naltrexol to naltrexone were also examined in a microsomal preparation. RESULTS: The Vmax, Km and CLint values for the formation of 6 beta-naltrexol from naltrexone were in the ranges of 16-45 nmol mg-1 protein h-1, 17-53 microM and 0.3-2.2 ml h-1 mg-1 protein, respectively. The steroid hormones testosterone (Ki = 0.3 +/- 0.1 microM) and dihydrotestosterone (Ki = 0.7 +/- 0.4 microM) were the most potent competitive inhibitors of 6 beta-naltrexol formation, with naloxone, menadione and corticosterone also producing > 50% inhibition at a concentration of 100 microM. The opioid agonists morphine, oxycodone, oxymorphone and hydromorphone, and a range of benzodiazepines showed < 20% inhibition at 100 microM. In the microsomal preparation, there was no formation of naltrexone from 6beta-naltrexol nor any formation of 6beta-naltrexol from naltrexone. CONCLUSIONS: The intersubject variability in the kinetic parameters of 6beta-naltrexol formation could play a role in the efficacy of and patient compliance with naltrexone treatment. This variability could be due in part to a genetic polymorphism of the dihydrodiol dehydrogenase DD4, one of the enzymes reported to be responsible for the formation of 6beta-naltrexol from naltrexone. DD4 also has hydroxysteroid dehydrogenase activity which could account for the potent inhibition by the steroid hormones testosterone and dihydrotestosterone. The clinical significance of the latter finding remains to be established. (+info)
Morphine and alternative opioids in cancer pain: the EAPC recommendations.
An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated. (+info)
I.v. ketoprofen for analgesia after tonsillectomy: comparison of pre- and post-operative administration.
We have evaluated the safety and efficacy of ketoprofen during tonsillectomy in 106 adults receiving standardized anaesthesia. Forty-one patients received ketoprofen 0.5 mg kg(-1) at induction ('pre' ketoprofen group) and 40 patients after surgery ('post' ketoprofen group), in both cases followed by a continuous ketoprofen infusion of 3 mg kg(-1) over 24 h; 25 patients received normal saline (placebo group). Oxycodone was used for rescue analgesia. Patients in the ketoprofen groups experienced less pain than those in the placebo group. There was no difference between the study groups in the proportion of patients who were given oxycodone during the first 4 h after surgery. However, during the next 20 h, significantly more patients in the placebo group (96%) received oxycodone compared with patients in the 'pre' ketoprofen group (66%) and the 'post' ketoprofen group (55%) (P=0.002). Patients in the placebo group received significantly more oxycodone doses than patients in the two ketoprofen groups (P=0.001). Two patients (5%) in the 'pre' ketoprofen group and one (3%) in the 'post' ketoprofen group had post-operative bleeding between 4 and 14 h. All three patients required electrocautery. (+info)
A rapid and sensitive high-performance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry method for the quantitation of oxycodone in human plasma.
A sensitive method for the determination of oxycodone concentrations in plasma by high-performance liquid chromatography (HPLC)-electrospray ionization-triple quadrupole mass spectrometry is described. The method is rugged, reliable, selective, and rapid with a run time of 2 min. One milliliter of plasma is made basic and extracted with 2-mL duplicate portions of 2% isoamyl alcohol in n-butyl chloride. The combined extracts are then evaporated to dryness, reconstituted in 100 microL of the mobile phase (15% methanol-85% water containing 0.1% acetic acid), and injected onto the HPLC. The limit of quantitation is 1 ng/mL, and the estimated limit of detection is 33 pg/mL (signal-to-noise = 3). Standard curves are linear over the range of 1 to 100 ng/mL with all correlation coefficient values greater than 0.9989. The method is used to determine the concentration of oxycodone in human plasma following the intravenous infusion of doses ranging from 5 to 15 mg in which the analysis of over 3000 plasma samples is required. (+info)
The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid.
Recently, the abuse of prescription opiates as alternatives to heroin has become a national concern. The determination of a six-drug opiate panel, codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, and oxycodone, in hair and oral fluid using solid-phase extraction and capillary gas chromatography-mass spectrometry (GC-MS) is described. Oral fluid was obtained from the donor by insertion of absorptive collectors into the mouth. Hair was collected from the patient and powdered using stainless steel ball bearings in a mini bead-beater apparatus. Opiates present in the samples were extracted from a buffered, aqueous matrix using a solid-phase cartridge. The extracts were concentrated and the methoxime/BSTFA derivatives prepared in order to eliminate interference from the keto-opiates. The extracts were separated by GC-MS in electron impact mode. By utilizing methoxyamine, we were able to produce the methoxime derivatives required for single derivative production and chromatographically separate all six opiates. The routine analysis of these opiates in hair and oral fluid using GC-MS is described for the first time. (+info)