Rilmenidine is an alpha 2 adrenoreceptor agonist used in the treatment of mild and moderate hypertension. In this study, a fast and accurate liquid chromatographic method with tandem mass spectrometric detection has been validated in order to assure quantification of rilmenidine in human serum. The fragmentation pathway of protonated rilmenidine was studied using high-resolution mass spectrometry (HRMS). This study compared selectivity, linearity, accuracy, precision, extraction efficiency, matrix effect and sensitivity using common liquid-liquid extraction (LLE) and solid-phase extraction (SPE) procedures. The limit of quantitation for both extraction techniques was 0.1 ng/ml. Several differences between the LLE and SPE have been observed in terms of linearity, accuracy, precision and matrix effect. Additionally, the advantages of SPE included less manual work load and increased recovery of rilmenidine in human serum to approximately 80% (LLE, 57%). The developed method involving SPE was found to be accurate (relative error (RE) < 5%), reproducible (relative standard deviation, RSD < 7%), robust and suitable for quantitative analysis of rilmenidine in serum samples obtained from patients under antihypertensive treatment.
- MeSH
- Antihypertensive Agents blood chemistry pharmacokinetics MeSH
- Chromatography, Liquid methods MeSH
- Solid Phase Extraction MeSH
- Humans MeSH
- Least-Squares Analysis MeSH
- Oxazoles blood chemistry pharmacokinetics MeSH
- Reproducibility of Results MeSH
- Rilmenidine MeSH
- Sensitivity and Specificity MeSH
- Drug Stability MeSH
- Tandem Mass Spectrometry methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Antihypertensive Agents MeSH
- Oxazoles MeSH
- Rilmenidine MeSH
1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. 4. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. 5. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.
- Keywords
- Biotransformation in rats, GC–MS, LC-HRMS, MDAI, new designer drugs, urinary metabolites,
- MeSH
- Indans urine MeSH
- Rats MeSH
- Substance Abuse Detection methods MeSH
- Illicit Drugs urine MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 5,6-methylenedioxy-2-aminoindane MeSH Browser
- Indans MeSH
- Illicit Drugs MeSH
An increasing microbial resistance to known antibiotics raises a demand for new antimicrobials. In this study the antimicrobial properties of a series of new N-Alkylpyridinium quaternary ammonium compounds (QACs) with varying alkyl chain lengths were evaluated for several nosocomial pathogens. The chemical identities of the new QACs were determined by NMR, LC-MS, and HRMS. All the planktonic bacteria tested were susceptible to the new QACs as evaluated by MIC and MBC assays. The antimicrobial effect was most pronounced against Staphylococcus aureus clinical isolates. Live/dead staining CLSM was used to test the effectiveness of the QACs in biofilms. The effectiveness was up to 10-fold lower than in the plankton. When QACs were used as irrigants in Er:YAG - SSP photoacoustic steaming, their effectiveness significantly increased. The combined use of irrigants and photoacoustic streaming increased biofilm removal from the surface and increased the killing rate of the cells remaining on the surface. This may allow for a shorter chemical exposure time and lower dosage of QACs used in applications. The results demonstrate that the new QACs have potential to be applied as antibacterial compounds effective against planktonic and biofilm bacteria as well as irrigants in removal of difficult-to-reach biofilms.
- Keywords
- antimicrobial activity, bacteria, biofilm, photoacoustic irrigation, quaternary ammonium salts,
- Publication type
- Journal Article MeSH
In Italy a particularly valuable chestnut is "Marrone di Roccadaspide", a protected geographical indication (PGI) product, deriving from a Castanea sativa cultivar, typical of Salerno province in Campania region. As chestnut industrial processes yield a large amount of shell by-products, in this study the possibility to retrain this waste food as potential source of bioactives was investigated. The ability of "Marrone di Roccadaspide" shell MeOH extract to modulate the pro-inflammatory transcriptional factor NF-κB after LPS stimulation, along with the antioxidant activity by a cell-based in vitro test, were evaluated. To correlate the NF-κB inhibition (67.67% at 5 μg/mL) and the strong antioxidant activity to the chemical composition, an analytical approach based on LC-ESI/LTQOrbitrap/MS/MSn along with NMR characterization of isolated compounds was developed. The identification of hydrolysable and condensed tannins, along with flavonoids, phenol glucosides, ellagic acid derivatives, and triterpenoids was accomplished. The most representative compounds were quantitatively analyzed by LC-ESI/QTrap/MS/MS, showing bartogenic acid as the compound occurring in the highest amount (103.08 mg/100 g shells). With the aim to explore the possibility to employ chestnut shells as suitable source of bioactives for the preparation of functional ingredients, the chemical composition and the antioxidant activity of "eco-friendly" extracts (EtOH and EtOH:H2O 7:3) was finally evaluated, showing a high superimposability of the EtOH:H2O (7:3) extract to the MeOH extract.
- Keywords
- Antioxidant activity, LC-HRMS/MS(n), Shells, Tannins, Triterpenes, “Marrone di Roccadaspide” PGI, “green” extracts,
- MeSH
- Antioxidants analysis MeSH
- Fagaceae chemistry MeSH
- Phenols analysis MeSH
- Flavonoids analysis MeSH
- Glucosides analysis MeSH
- Evaluation Studies as Topic MeSH
- Hydrolyzable Tannins analysis MeSH
- Calibration MeSH
- Ellagic Acid analysis MeSH
- Humans MeSH
- NF-kappa B metabolism MeSH
- Nuts chemistry MeSH
- Proanthocyanidins analysis MeSH
- Cell Proliferation MeSH
- Rationalization * MeSH
- Reactive Oxygen Species MeSH
- Plant Extracts analysis MeSH
- Tandem Mass Spectrometry MeSH
- Tannins analysis MeSH
- Triterpenes analysis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Italy MeSH
- Names of Substances
- Antioxidants MeSH
- bartogenic acid MeSH Browser
- Phenols MeSH
- Flavonoids MeSH
- Glucosides MeSH
- Hydrolyzable Tannins MeSH
- Ellagic Acid MeSH
- NF-kappa B MeSH
- Proanthocyanidins MeSH
- Reactive Oxygen Species MeSH
- Plant Extracts MeSH
- Tannins MeSH
- Triterpenes MeSH
Recreational use of the potent synthetic opioid 3,4- dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700) is rising, accompanied by increasingly frequent cases of serious intoxication. This article reports a case of near-fatal U-47700 intoxication. A man was found unconscious (with drug powder residues). After 40 h in hospital (including 12 h of supported ventilation), he recovered and was discharged. Liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or gas chromatography/mass spectrometry (GC/MS) were used to detect and quantify substances in powders, serum and urine. Powders contained U-47700 and two synthetic cannabinoids. Serum and urine were positive for U-47700 (351.0 ng/mL), citalopram (
- Keywords
- 3,4- dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide, U47700, clonazolam, forensic science, forensic toxicology, novel benzodiazepine, novel psychoactive substance, synthetic opioid,
- MeSH
- Benzamides adverse effects analysis MeSH
- Benzodiazepines analysis MeSH
- Chromatography, Liquid MeSH
- Citalopram analysis MeSH
- Adult MeSH
- Mass Spectrometry MeSH
- Humans MeSH
- Midazolam analysis MeSH
- Substance Abuse Detection MeSH
- Gas Chromatography-Mass Spectrometry MeSH
- Drug Overdose * MeSH
- Forensic Toxicology MeSH
- Illicit Drugs adverse effects analysis MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Benzamides MeSH
- Benzodiazepines MeSH
- Citalopram MeSH
- Midazolam MeSH
- U-47700 MeSH Browser
- Illicit Drugs MeSH
