Determination of acamprosate in human plasma by UPLC-MS/MS: Application to therapeutic drug monitoring.

Acamprosate is a medication used to treat alcohol dependence. Therapeutic drug monitoring is important in drugs for the treatment of substance-related disorders. Therefore, in this study, a new selective, very simple and rapid ultra-performance liquid chromatography-tandem mass spectrometer method was developed for the therapeutic drug monitoring of acamprosate. The developed method allows the determination of acamprosate in human plasma. The method was validated in terms of selectivity and linearity, which was in the range of 100-1,200 ng/ml for acamprosate. Intra-assay and inter-assay accuracy and precision were within the acceptable limits of the Eueopean Medicines Agency guideline. The lower limit of quantitation was 100 ng/ml for acamprosate. The developed method was successfully applied for therapeutic drug monitoring in patient plasma samples.

Chemical and molecular characterization of metabolites from Flavobacterium sp.

In this study, a Flavobacterium sp. is isolated from natural spring, and identified using molecular techniques. Extracellular and intracellular secondary metabolites are identified using solid phase microextraction gas chromatography-mass spectrometry and ultra performance liquid chromatography. Cytotoxic activity of the extracellular compounds produced by the Flavobacterium sp. and quercetin as the standard are measured using ECV304 human endothelial cells in vitro. Our results show that Flavobacterim sp. isolate has the highest percentage of similarity with Flavobacterium cheonhonense strain ARSA-15 (99%). Quercetin is detected as the major extracellular compound produced by the Flavobacterium sp. Methanol extract of Flavobacterium sp. resulted in a higher cell viability results when compared to DMSO extracts. Computational chemistry approach was used and it has been found that polar solvent (methanol) contributed to higher antioxidant activity. In conclusion, Flavobacterium sp. can be used to produce quercetin for industrial purposes.

Monitoring of neomycin sulfate antibiotic in microbial fuel cells.

Indirect detection and quantification of the neomycin sulfate antibiotic was accomplished in microbial fuel cells. Performance of the microbial fuel cells was examined on the basis of the following parameters; voltage generation, power density, current density and coulombic efficiencies. Removal of neomycin sulfate was monitored using LC-MS/MS in parallel with chemical oxygen demand and total carbohydrate removal. While neomycin sulfate was partially degraded, microbial fuel cell performance appeared to be affected and eventually inhibited by neomycin sulfate on a concentration-based fashion. In order to further examine the neomycin sulfate bio-sensing activity of the microbial fuel cell, a computational chemistry approach was used to obtain the information about the highest occupied molecular orbital-lowest unoccupied molecular orbital energy values of outer electron orbitals, their distribution, and ionization potentials (IPs). The results showed that electroactive bio-film-based MFCs can be used for sensitive detection of neomycin sulfate found in wastewaters.

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

BACKGROUND: There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. METHODS: The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. RESULTS: Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. CONCLUSIONS: Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.