Determination of salmeterol, α-hydroxysalmeterol and fluticasone propionate in human urine and plasma for doping control using UHPLC-QTOF-MS.

Salmeterol and fluticasone are included in the Prohibited List annually issued by the World Anti-Doping Agency. While for other permitted beta-2 agonists a threshold has been established, above which any finding constitutes an Adverse Analytical Finding, this is not the case with salmeterol. The salmeterol metabolite, α-hydroxysalmeterol, has been described as a potentially more suitable biomarker for the misuse of inhaled salmeterol.

Official International Association for Therapeutic Drug Monitoring and Clinical Toxicology Guideline: Development and Validation of Dried Blood Spot-Based Methods for Therapeutic Drug Monitoring.

Dried blood spot (DBS) analysis has been introduced more and more into clinical practice to facilitate Therapeutic Drug Monitoring (TDM). To assure the quality of bioanalytical methods, the design, development and validation needs to fit the intended use. Current validation requirements, described in guidelines for traditional matrices (blood, plasma, serum), do not cover all necessary aspects of method development, analytical- and clinical validation of DBS assays for TDM.

Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry for Therapeutic Drug Monitoring of Metformin and Rosuvastatin in Human Plasma.

In this work a hydrophilic interaction liquid chromatography/positive ion electrospray mass spectrometric assay (HILIC/ESI-MS) has been developed and fully validated for the quantitation of metformin and rosuvastatin in human plasma. Sample preparation involved the use of 100 μL of human plasma, following protein precipitation and filtration. Metformin, rosuvastatin and 4-[2-(propylamino) ethyl] indoline 2 one hydrochloride (internal standard) were separated by using an X-Bridge-HILIC BEH analytical column (150.

The impact of nutrition education on nutrition knowledge and adherence to the Mediterranean Diet in adolescent competitive swimmers.

Objectives: Nutrition education of adolescent competitive swimmers is under-studied although their diet and nutrition knowledge are generally poor. This study aimed to assess the impact of nutrition education on nutrition knowledge and adherence to the Mediterranean Diet (MD) and explore the effect of parental education on the swimmers' MD adherence.

Design: A pre-post measurement interventional study was carried out.

Bioanalytical LC-MS Method for the Quantification of Plasma Androgens and Androgen Glucuronides in Breast Cancer.

The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS).

Development and validation of a LC/MS method for the determination of Δ(9)-tetrahydrocannabinol and 11-carboxy-Δ(9)-tetrahydrocannabinol in the larvae of the blowfly Lucilia sericata: Forensic applications.

In a number of forensic toxicological cases, Δ(9)-tetrahydrocannabinol (THC) and its metabolite 11-carboxy-delta-9-tetrahydrocannabinol (THCA) are frequently considered as contributor factors to the event. To that, a liquid chromatographic mass spectrometric method is described for the identification and quantitation of THC and its metabolite THCA in the forensically important larvae of L. sericata.

Multi-residue determination of 10 selected new psychoactive substances in wastewater samples by liquid chromatography-tandem mass spectrometry.

New psychoactive substances (NPSs) have become increasingly popular in recent years. The analysis of these substances in influent wastewater (IWW) can be used to track their use in communities. In addition, an evaluation of the amount of NPSs released to the aquatic environment can be performed through the analysis of effluent wastewater (EWW).

Highly sensitive determination of 68 psychoactive pharmaceuticals, illicit drugs, and related human metabolites in wastewater by liquid chromatography-tandem mass spectrometry.

The present work describes the development and validation of a highly sensitive analytical method for the simultaneous determination of 68 compounds, including illicit drugs (opiates, opioids, cocaine compounds, amphetamines, and hallucinogens), psychiatric drugs (benzodiazepines, barbiturates, anesthetics, antiepileptics, antipsychotics, antidepressants, and sympathomimetics), and selected human metabolites in influent and effluent wastewater (IWW and EWW) by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method involves a pre-concentration and cleanup step, carried out by solid-phase extraction (SPE) using the adsorbent Strata-XC, followed by the instrumental analysis performed by LC-MS/MS, using a Kinetex pentafluorophenyl (PFP) reversed-phase fused-core column and electrospray ionization (ESI) in both positive and negative modes. A systematic optimization of mobile phases was performed to cope with the wide range of physicochemical properties of the analytes.

Stability of morphine, codeine, and 6-acetylmorphine in blood at different sampling and storage conditions.

The stability of drugs in biological specimens is a major concern during the evaluation of the toxicological results. The stability of morphine, codeine, and 6-acetyl-morphine in blood was studied after different sampling conditions: (i) in glass, polypropylene or polystyrene tubes, (ii) with addition of dipotassium ethylene diamine tetraacetic acid (K2EDTA) or sodium oxalate (Na2C2O4), and (iii) with or without the addition of sodium fluoride (NaF). Spiked blood samples were stored at two different temperatures (4 and -20°C), analyzed after different storage times and after three freeze–thaw cycles.

The clavicle bone as an alternative matrix in forensic toxicological analysis.

Although human blood is the reference medium in the field of forensic toxicology, alternative matrices may be required when traditional specimens are not available, especially in the investigation of cases involving decomposing remains. Clavicle bone may provide an appropriate sample of choice since it can easily be obtained at autopsy after the removal of the breastplate for the inspection of the thoracic viscera. To the author's knowledge, this is the first time that clavicle bone is used as an alternative matrix for the detection of drugs.

A validated GC/MS method for the determination of amisulpride in whole blood.

A sensitive GC/MS method for the determination of amisulpride in whole blood was developed, optimized and validated. Sample preparation included solid-phase extraction using HF Bond Elut C18 cartridges and further derivatization with heptafluorobutyric anhydride (HFBA). The limits of detection and quantification were 3.

Hydrophilic interaction liquid chromatography/positive ion electrospray ionization mass spectrometry method for the quantification of alprazolam and α-hydroxy-alprazolam in human plasma.

A hydrophilic interaction liquid chromatography/positive ion electrospray-mass spectrometry (HILIC-ESI/MS) has been developed and fully validated for the quantification of alprazolam and its main metabolite, α-hydroxy-alprazolam, in human plasma. The assay is based on 50μL plasma samples, following liquid-liquid extraction. All analytes and the internal standard (tiamulin) were separated by hydrophilic interaction liquid chromatography using an X-Bridge-HILIC analytical column (150.

Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry: could it raise new perspectives in the diagnostic field of hormone-dependent malignancies?

Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues.

Direct urine analysis for the identification and quantification of selected benzodiazepines for toxicology screening.

A simple and rapid LC/MS method with direct injection analysis was developed and validated for the identification and quantification of ten benzodiazepines (flunitrazepam, nordiazepam, diazepam, 7-aminoflunitrazepam, flurazepam, bromazepam, midazolam, alprazolam, temazepam and oxazepam) in human urine using diazepam-d5 as internal standard (IS). The main advantage of the proposed methodology is the minimal sample preparation procedure, as diluted urine samples were directly injected into LC/MS system. Electrospray ionization in positive mode using selected ion monitoring was chosen for the identification and quantification of the analytes.

A fully validated method for the simultaneous determination of 11 antidepressant drugs in whole blood by gas chromatography-mass spectrometry.

Antidepressant drugs are widely used for the treatment of depression and other psychiatric disorders and as a result they are involved in numerous clinical and forensic cases. The aim of this study was the development, optimization and validation of a simple, specific and sensitive GC/MS method for the simultaneous determination of 11 antidepressant drugs and 4 of their metabolites (amitriptyline, citalopram, clomipramine, fluoxetine, fluvoxamine, maprotiline, desmethyl-maprotiline, mirtazapine, desmethyl-mirtazapine, nortriptyline, paroxetine, sertraline, desmethyl-sertraline, venlafaxine and desmethyl-venlafaxine) in whole blood. The combination of solid-phase extraction with derivatization using heptafluorobutyric anhydride efficiently reduced matrix effect and improved sensitivity of the method.

Development and validation of a simple GC-MS method for the simultaneous determination of 11 anticholinesterase pesticides in blood--clinical and forensic toxicology applications.

Anticholinesterase pesticides are widely used, and as a result they are involved in numerous acute and even fatal poisonings. The aim of this study was the development, optimization, and validation of a simple, rapid, specific, and sensitive gas chromatography-mass spectrometry method for the determination of 11 anticholinesterase pesticides (aldicarb, azinphos methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, methamidophos, methidathion, methomyl, and terbufos) in blood. Only 500 μL of blood was used, and the recoveries after liquid-liquid extraction (toluene/chloroform, 4:1, v/v) were more than 65.

Migration study of 1,3-butadiene in eye-drop solutions.

The potential deleterious effects of extractables/leachables in pharmaceutical products led the USP, EP, and JP to require extractable and toxicity testing of container/closure systems. To that, a headspace gas chromatography flame ionization detection method was developed and validated for the determination of 1,3-butadiene (1,3-BD) as a potential extractable residue from a pharmaceutical container/closure system into eye-drop solutions. A migration study was further applied in eight eye-drop solutions (currently marketed products) after short- and long-term exposure of these products at various temperatures.

Naphyrone: a "legal high" not legal any more.

Naphyrone, also known as naphthylpyrovalerone and O-2482, is a cathinone derivative that has been recently advertized for purchase on a number of websites. Naphyrone belongs to a new class of "designer drugs" that has emerged on the drugs abuse market and has gained popularity as the new "legal high." Legal highs have been circulating for a number of years in Europe and are becoming popular in the United States.

A simple and sensitive GC/MS method for the determination of atropine during therapy of anticholinesterase poisoning in serum samples.

Atropine is used in the daily clinical practice for the treatment of poisonings caused by anticholinesterase pesticides, due to its sympathomimetic action. The investigation of the cause of the adverse effects that appear during atropine administration showed the necessity for the development and validation of a simple, rapid, sensitive, and specific method for the determination of atropine levels in serum samples. The developed method includes liquid-liquid extraction with ethyl acetate: dichloromethane (3:1, v/v) and derivatization using N,O-bis(trimethylsilyl)-trifluoracetamide (BSTFA) with 1% trimethylchlorsilane (TMCS) in acetonitrile environment.

Development and validation of a gas chromatography-mass spectrometric method for the determination of sildenafil and desmethyl-sildenafil in whole blood.

Sildenafil (SDL) is a phosphodiesterase type 5 inhibitor and it is approved for the treatment of erectile dysfunction and pulmonary hypertension. SDL is extensively metabolized to its pharmacologically active metabolite, desmethyl-sildenafil (DSDL). A sensitive and specific GC/MS method for the determination of SDL and DSDL in whole blood was developed and validated to support therapeutic drug monitoring of SDL patients.

Development and validation of an EI-GC/MS method for the determination of sertraline and its major metabolite desmethyl-sertraline in blood.

A sensitive and specific GC/MS method for the determination of sertraline and its main metabolite desmethyl-sertraline in whole blood has been developed, optimized and validated. Sample preparation included solid-phase extraction of both analytes and their derivatization with heptafluorobutyric anhydride (HFBA). Protriptyline was used as internal standard for the determination of both analytes.

Development and validation of a method for the determination of buprenorphine and norbuprenorphine in breast milk by gas chromatography-mass spectrometry.

Buprenorphine (BUP) is used for the maintenance of opioid-addicted pregnant women. Because BUP and its main metabolite nor-BUP are excreted into breast milk, a sensitive and specific GC/MS method has been developed, optimized and validated for their determination in breast milk. BUP-d4 was used as internal standard.

Development and validation of a GC/MS method for the determination of tadalafil in whole blood.

Tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor and it is used in the treatment of pulmonary arterial hypertension and erectile dysfunction. A sensitive and specific method is described for the determination of tadalafil in whole blood. Tadalafil and its internal standard (protriptyline) were isolated from the matrix by solid phase extraction, and were analyzed by gas chromatography/mass spectrometry (GC/MS) after derivatization by N,O-bis(trimethylsilyl)-trifluoracetamide (BSTFA) with 1% trimethylchlorsilane (TMCS).

A fully validated method for the determination of vardenafil in blood using gas chromatography/mass spectrometry.

Vardenafil (VDN) is one of the three commercially available phosphodiesterase type 5 inhibitors and it is mainly used in the treatment of erectile dysfunction. A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method for the determination of VDN in blood has been developed and validated. Sample preparation included solid-phase extraction and derivatization with N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA) and 1% tert-butyldimethylsilylchloride (TBDMSCl).

Development and validation of a highly sensitive GC/MS method for the determination of buprenorphine and nor-buprenorphine in blood.

A sensitive and specific GC/MS method for the determination of buprenorphine (BPN) and its main metabolite nor-buprenorphine (nor-BPN) in blood has been developed, optimized and validated. Sample preparation includes solid-phase extraction of both analytes and their derivatization with acetic anhydride in pyridine. BPN-d4 was used as internal standard for the determination of both analytes.