1,721,187 research outputs found
Novel Atypical Antipsychotics: Metabolism and Therapeutic Drug Monitoring (TDM)
No full textMedicinal chemistry is continually developing and testing new drugs and drug candidates to satisfactorily address the needs of patients suffering from schizophrenia. In the last few years, some significant additions have been made to the list of widely available atypical antipsychotics. In particular, iloperidone, asenapine and lurasidone have been approved by the USA's Food and Drug Administration in 2009-10. In this paper, the most notable metabolic characteristics of these new drugs are addressed, with particular attention to their potential for pharmacokinetic interactions, and to the respective advantages and disadvantages in this regard. Moreover, current perspectives on the therapeutic drug monitoring (TDM) of the considered drugs are discussed. Since TDM is most valuable when it allows the personalisation and optimisation of therapeutic practices, it is even more interesting in the case of novel drugs, such as those discussed here, whose real impact in terms of side and toxic effects on very large populations is still unknown. Some analytical notes, related to TDM application, are included for each drug
On the benefits of therapeutic drug monitoring for patients undergoing treatment with antipsychotic agents
No full textPerspectives and strategies for anti-doping analysis
No full textBioanalysis is continually evolving and reaching new goals. Within this unending process, anti-doping analysis follows its own trajectory, but cannot go forward alone and has to use all of the bioanalytical strategies and tools, adapting them to sport testing. Among these, biological matrix choice is one of the most important weapons. Samples alternative to blood and urine have to be considered, since they can provide complementary information, or specifically accumulate some substances. Dried miniaturized matrices have substantial advantages over wet ones, such as a generally better stability at room temperature and consequently more favorable behavior during storage and transportation. For these reasons, dried microsampling and MS analysis represent probably the best prospect to become one of the golden standards at the forefront of anti-doping bioanalysis research. Coupling this setup with sample pretreatment and analysis automation and miniaturization could produce important progress in this field
Microsampling and LC-MS/MS for antidoping testing of glucocorticoids in urine
Full text linkBackground. Systemic glucocorticoids are prohibited in-competition by the World Anti-Doping Agency. Here, we describe an original microsampling workflow for the quantitation of three endogenous (cortisol, corticosterone and cortisone) and three exogenous (dexamethasone, methylprednisolone and fludrocortisone) corticosteroids in 30 μl of human urine. Materials & methods. Microsampling was carried out by dried urine spot (DUS) sampling and volumetric absorptive microsampling (VAMS), followed by solvent extraction and LC-MS/MS analysis. Results & conclusion: Good linearity (r2 > 0.9989) was obtained for all analytes; extraction yields (>81%), precision (RSD < 8.6%) and matrix effect (<12%) were satisfactory. Microsample stability at room temperature was good (analyte loss <15% after 3 months). Data obtained from real urine microsample analysis were compared with those of fluid urine, providing very good agreement (r2 > 0.9991)
Tutorial: Volumetric absorptive microsampling (VAMS)
No full textVolumetric absorptive microsampling (VAMS) is a recent microsampling technique used to obtain dried specimens of blood and other biological matrices for application to a plethora of bioanalytical purposes. As such, it can be likened to dried blood spot (DBS) technique that has been in wide use for the last 40 years. However, VAMS promises to bring some significant advantages over DBS, related to sampling volume accuracy, haematocrit (HCT) dependence, pre-treatment and automation. Although some aspects still need to be investigated in depth, VAMS is increasingly recognised as a viable alternative to DBS and other dried microsampling techniques. In this tutorial, different aspects of VAMS approach are described and discussed, presenting the procedures adopted and the results obtained by those authors who have developed this kind of analytical workflow in the last few years. Hopefully, this will help other scientists to find new solutions to old and recent problems related to microsampling and to produce new, sound and interesting science in this field
Metabolism of Drugs Used In the Therapy of Seizures: An Analytical Point Of View. PART 1
No full textSeizures are aetiologically and clinically heterogeneous neurological disorders that are currently treated using a wide array of drugs, belonging to equally heterogeneous chemical classes. Some of them are known as "antiepileptic drugs" (AEDs), due to their main field of use, while others (such as benzodiazepines) are frequently used for other conditions as well as for seizures. Due to their different chemical properties and mechanisms of activity, the metabolic characteristics of anti-seizure drugs can vary widely, also producing big differences in terms of safety, efficacy and therapeutic suitability
Enantioselective analysis of the methamphetamine precursors ephedrine and pseudoephedrine by capillary electrokinetic chromatography using cyclodextrins as chiral selectors
Full text linkEphedrine and pseudoephedrine can be used as precursors for the illicit synthesis of stimulant drugs, such as methamphetamine and methcathinone. For this reason, an enantioselective capillary electrokinetic chromatography method was developed for the separation of ephedrine and pseudoephedrine enantiomers. After testing two different charged or chargeable cyclodextrins (-cyclodextrin sulphate and carboxymethyl--cyclodextrin) and a few mixtures as possible chiral selectors, a mixture of 3 mM carboxymethyl--cyclodextrin and 3 mM heptakis(2,6-di-O-methyl)--cyclodextrin in pH 3.4 acetate buffer was used as the enantioselective background electrolyte and the separation was carried out in an uncoated silica capillary (75 μm internal diameter, 48.6 cm total length, 40.0 cm effective length). Analytical method performance was then evaluated in terms of linearity, precision, selectivity and accuracy with good results. Proof of concept application to mixtures simulating illicit methamphetamine (containing small amounts of ephedrine and pseudoephedrine as possible residual synthesis impurities) provided satisfactory results for the identification and quantitation of the four analyte diastereomers
Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption
Full text linkReliable, feasible analytical methods are needed for forensic and anti-doping testing of cocaine and its most important metabolites, benzoylecgonine, ecgonine methyl ester, and cocaethylene (the active metabolite formed in the presence of ethanol). An innovative workflow is presented here, using minute amounts of dried blood or plasma obtained by volumetric absorptive microsampling (VAMS), followed by miniaturized pretreatment by dispersive pipette extraction (DPX) and LC-MS/MS analysis. After sampling 20 μL of blood or plasma with a VAMS device, the sample was dried, extracted, and loaded onto a DPX tip. The DPX pretreatment lasted less than one minute and after elution with methanol the sample was directly injected into the LC-MS/MS system. The chromatographic analysis was carried out on a C8 column, using a mobile phase containing aqueous formic acid and acetonitrile. Good extraction yield (> 85%), precision (relative standard deviation, RSD < 6.0%) and matrix effect (< 12%) values were obtained. Analyte stability was outstanding (recovery > 85% after 2 months at room temperature). The method was successfully applied to real blood and plasma VAMS, with results in very good agreement with those of fluid samples. The method seems suitable for the monitoring of concomitant cocaine and ethanol use by means of plasma or blood VAMS testing
New-Generation, non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs
No full textNew-generation antidepressants (NGAs) are the latest additions to the clinician's arsenal in the fight against depression. After the introduction of selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups followed, identified by their main mechanisms of activity: serotonin and norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators (SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and selective serotonergic antidepressants (NaSSA); norepinephrine reuptake inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors (SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists (MaSA). Although SSRIs are still the most widely used and well known NGAs, the other groups are increasingly being used in the current therapeutic settings obtaining comparable clinical results, and with tolerability and safety profiles that can often provide significant advantages over those of SSRIs
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