An analytical procedure was evaluated for the comprehensive toxicological screening of drugs, metabolites, and pesticides in 1-mL urine samples by TurboIon spray liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) in the positive ionization mode and continuous mass measurement. The substance database consisted of exact monoisotopic masses for 637 compounds, of which an LC retention time was available for 392. A macroprogram was refined for extracting the data into a legible report, utilizing metabolic patterns and preset identification criteria. These criteria included +/-30 ppm mass tolerance, a +/-0.2-min window for absolute retention time, if available, and a minimum area count of 500. The limit of detection, determined for 90 compounds, was <0.1 mg/L for 73% of the compounds studied and >1.0 mg/L for 6% of the compounds. For method comparisons, 50 successive autopsy urine samples were analyzed by this method, and the results confirmed by gas chromatography/mass spectrometry (GC/MS). Findings for parent drugs were consistent with both methods; in addition, LC/TOFMS regularly revealed apparently correct findings for metabolites not shown by GC/MS. Mean and median mass accuracy by LC/TOFMS was 7.6 and 5.4 ppm, respectively. The procedure proved well-suited for tentative identification without reference substances. The few false positives emphasized the fact that all three parameters, exact mass, retention time, and metabolite pattern, are required for unequivocal identification.
The pharmacokinetics of intravenous oxycodone in children aged 6-93 months are fairly similar to those reported in adults. Intramuscular administration provides relatively constant drug absorption, but after buccal and gastric administration the interindividual variation in the rate and extent of absorption is large.
The analgesic concentrations of oxycodone in acute post-operative pain management have not been established. Here, we have evaluated the minimum effective concentration (MEC) and the minimum effective analgesic concentration (MEAC) of oxycodone in pain after laparoscopic cholecystectomy (LCC) in 23 adult patients. The patients were provided with 0.1 mg ⁄ kg of oxycodone i.v. 10-15 min. before the end of surgery. After surgery, when the wound pain at rest was ‡3 ⁄ 10 and ⁄ or ‡5 ⁄ 10 during wound compression, a first blood sample was obtained (MEC). A second blood sample was obtained after titration with 2 mg i.v. of oxycodone to wound pain <3 ⁄ 10 at rest and <5 ⁄ 10 during wound compression (MEAC). A third blood sample was obtained at the recurrence of the wound pain (the second MEC), and the final blood sample when pain relief was obtained a second time (the second MEAC). At the first onset of pain (MEC), mean P-oxycodone was 21 ng ⁄ mL (95% CI 13-29 ng ⁄ mL). At the first pain relief (MEAC), P-oxycodone was 55 ng ⁄ mL (19-91 ng ⁄ mL). The second MEC was 34 ng ⁄ mL (11-57 ng ⁄ mL), and the second MEAC was 47 ng ⁄ mL (14-80 ng ⁄ mL). In conclusion, the estimated MEC, 20-35 ng ⁄ mL, and MEAC, 45-50 ng⁄ mL, values of P-oxycodone in patients after LLC were significantly higher than those proposed previously. Early pain after LCC appeared to be a feasible method to estimate the analgesic efficacy of oxycodone in acute pain management.
Hair analysis in forensic and clinical toxicology has been strongly focused on drugs of abuse, and comprehensive, drug class-independent screening methods based on mass spectrometric detection have not been applied to date. In this study, a qualitative drug screening method by liquid chromatography coupled to time-of-flight mass spectrometry, earlier developed and evaluated for forensic toxicological urine analysis, was adapted for screening of basic drugs in hair. The method included alkaline hydrolysis, purification with mixed-mode solid phase extraction, and analysis by liquid chromatography coupled to time-of-flight mass spectrometry with automated data analysis and reporting. Identification was based on accurate mass, isotopic pattern fit, and retention time, if available. Analysis of 32 hair samples from deceased drug addicts revealed 35 different drugs. The drug classes identified included antidepressants, antipsychotics, antiepileptics, amphetamines, opioids, beta-blockers, a benzodiazepine, a hypnotic, a local anesthetic, an antiemetic, and an antipyretic analgesic. The findings were in good agreement with the findings in blood and urine by other methods. Moreover, information about previous drug use not evident in the analysis of other matrices was obtained in the majority (72%) of the cases. Tramadol was an especially predominant finding, suggesting tramadol abuse as an opioid substitute. One apparent false-positive finding was identified. The mean and median mass accuracies of positive findings were 2.3 and 1.8 ppm, corresponding to 0.5 and 0.4 mDa, respectively. Cutoff values for tramadol and methamphetamine in hair were 100 and 200 pg/mg, respectively. The method proved to be a simple and straightforward tool for comprehensive screening of basic drugs in hair.
We present here the first mass spectroscopic (MS) identification of the main tamoxifen-induced DNA adducts in rat liver. The two main adducts were isolated by high-performance liquid chromatography (HPLC) and identified by MS, MS-MS and ultraviolet spectroscopy. Adduct 1 was the N-desmethyltamoxifen-deoxyguanosine adduct in which the alpha-position of the metabolite N-desmethyltamoxifen is linked covalently to the amino group of deoxyguanosine. Adduct 2 was confirmed to be the trans isomer of alpha-(N2-deoxyguanosinyl)tamoxifen, as previously suggested by co-chromatography.
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