Amikacin therapeutic drug monitoring: Evaluation of therapy performance and analytical techniques in a developing country setting.

Introduction: Healthcare systems face several challenges, with microbial infections being one of the main concerns. Therapeutic drug monitoring (TDM) is a strategy that has been encouraged to optimize antimicrobial regimens, particularly those with significant toxicity and narrow therapeutic indices, such as amikacin (AMK). We aimed to evaluate AMK concentrations of patients in a non-routine TDM setting and compare the performance of immunoassay and chromatography methods for routine clinical use.

Determination of drugs of abuse and metabolites in plasma microsamples by LC-MS/MS after microQuEChERS extraction.

Identifying drugs of abuse and their metabolites in plasma is vital in both forensic and clinical toxicology. While the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method offers an efficient approach to sample preparation, its application is complex due to the wide-ranging properties of target analytes and the challenges posed by biological matrix interferences. This study aims to develop a microQuEChERS approach for the quantification of 14 drugs of abuse and metabolites utilizing minimal sample and solvent volumes.

Comparison of vancomycin assays in patients undergoing hemodialysis.

Vancomycin is a glycopeptide antibiotic mainly excreted by glomerular filtration. Therefore, patients undergoing hemodialysis tend to accumulate its crystalline degradation product, which has been associated with cross-reaction in commercial immunoassays. The aim of this study was to assess the performance of two commercial immunoassays for measuring vancomycin levels in patients undergoing hemodialysis.

Determination of meropenem in capillary plasma microsamples using LC-MS/MS.

The measurement of meropenem plasma concentrations is employed for dosing regimen individualization. The aim of this study was to develop and validate a LC-MS/MS assay for quantification of meropenem in capillary plasma microsamples. Samples were prepared by protein precipitation with acetonitrile, followed by clean-up with dichloromethane.

Risk assessment of a Brazilian urban population due to the exposure to pyrethroid insecticides during the COVID-19 pandemic using wastewater-based epidemiology.

Pyrethroids are synthetic insecticides commonly used in agriculture and homes due to their low toxicity to mammals and effectiveness at low doses. However, exposure to pyrethroids can cause various symptoms, depending on the route of exposure. To measure human exposure to pyrethroids, researchers used wastewater-based epidemiology (WBE) with polar organic chemical integrative samplers (POCIS) sampling.

Evaluation of dried blood spots as an alternative sampling strategy for 5-fluorouracil monitoring: From method development to clinical application.

Therapeutic drug monitoring (TDM) of 5-Fluorouracil (5-FU) is strongly recommended because of its large inter-individual pharmacokinetic variability, narrow therapeutic window, and incidence of toxicity. However, there are several factors that limit the application of TDM in clinical settings. Considering the intrinsic advantages of dried microsamples, such as minimally invasive sampling, analyte stability, and cost-effective logistics, this study aimed to develop a method for the determination of 5-FU in dried blood spots (DBS) using ultra-high liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and to evaluate its clinical application.

Determination of amphetamines, opioids, cocaine metabolites and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in urine using biocompatible solid-phase microextraction and ultra-performance LC-MS/MS.

Workplace drug testing primarily relies on urine analysis, targeting multiple compounds with varying physicochemical characteristics. Biocompatible solid-phase microextraction (BioSPME) is a miniaturized solid-phase extraction technique that enables the simultaneous extraction and preconcentration of analytes directly from the biological matrix. The BioSPME procedure consisted of the sequential extraction of 50-μl urine samples using LC Tips C18 in basic and acidic pH, followed by desorption with methanol and -hexane, respectively.

Evaluation of hemaPEN sampling device for measurement of cocaine and metabolites in capillary blood by LC-MS/MS.

Dried blood spot sampling has been reported for on-site collection of specimens, but measurements are affected by blood hematocrit, and special handling is required, especially for forensic applications. The hemaPEN blood collection device was developed to produce spots with constant volume. Linearity between 1 and 500 ng/ml was shown for cocaine and the metabolites benzoylecgonine and cocaethylene.

Evaluation of UGT1A1 and CYP3A Genotyping and Single-Point Irinotecan and Metabolite Concentrations as Predictors of the Occurrence of Adverse Events in Cancer Treatment.

Purpose: The variability on irinotecan (IRI) pharmacokinetics and toxicity has been attributed mostly to genetic variations in the UGT1A1 gene, responsible for conjugation of the active metabolite SN-38. Also, CYP3A mediates the formation of inactive oxidative metabolites of IRI. The association between the occurrence of severe adverse events, pharmacokinetics parameters, and UGT1A1 and CYP3A4 predicted phenotypes was evaluated, as the evaluation of [SN-38]/IRI dose ratio as predictor of severe adverse events.

Long-term monitoring of drug consumption patterns during the COVID-19 pandemic in a small-sized community in Brazil through wastewater-based epidemiology.

The abuse of legal and illegal drugs is a global public health problem, also affecting the social and economic well-being of the population. Thus, there is a significant interest in monitoring drug consumption. Relevant epidemiological information on lifestyle habits can be obtained from the chemical analysis of urban wastewater.

Development and validation of an assay for the measurement of gentamicin concentrations in dried blood spots using UHPLC-MS/MS.

Gentamicin sulfate (GEN) is an aminoglycoside antibiotic with a narrow therapeutic range of plasma concentrations. The collection of venous blood represents a significant burden for patients, especially in neonatology. Dried blood spots (DBS) obtained from capillary blood can be an alternative for drug measurements in this particular population.

Sensitive determination of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and complementary cannabinoids in hair using alkaline digestion and mixed-mode solid phase extraction followed by liquid-chromatography-tandem mass spectrometry.

Hair drug testing can be used for the evaluation of cannabis use with a large detection window, and is required for professional driving license granting in Brazil. A positive hair result for cannabis use requires quantification of the metabolite THC-COOH above the cutoff value of 0.2 ng/g.

Determination of cortisol in hair using UHPLC-MS/MS: application to patients admitted for ethanol dependence treatment.

Cortisol hair levels can be used to evaluate chronic stress status. In this context, an improved UHPLC-MS/MS assay for the determination of cortisol in hair was developed and validated. Hair was extracted with methanol for 4 h at 25°C.

Sensitive determination of gentamicin in plasma using ion-exchange solid-phase extraction followed by UHPLC-MS/MS analysis.

Background: Therapeutic drug monitoring (TDM) of gentamicin sulfate (GEN) is usually recommended, particularly in critical patients. Only a few reports had described the determination of GEN in plasma or plasma using LC-MS/MS.

Objective: This study aimed to develop and validate a sensitive ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) assay for the quantification of GEN in small volumes of human plasma.

Evaluation of Illicit Drug Consumption by Wastewater Analysis Using Polar Organic Chemical Integrative Sampler as a Monitoring Tool.

Illicit drug abuse is a worldwide social and health problem, and monitoring illicit drug use is of paramount importance in the context of public policies. It is already known that relevant epidemiologic information can be obtained from the analysis of urban residual waters. This approach, named wastewater-based epidemiology (WBE), is based on the measurement of specific markers, resulting from human biotransformation of the target drugs, as indicators of the consumption of the compounds by the population served by the wastewater treatment installation under investigation.

Simple determination of valproic acid serum concentrations using BioSPME followed by gas chromatography-mass spectrometric analysis.

Valproic acid (VA) is a drug widely used on the treatment of epilepsy and bipolar affective disorders, with stablished therapeutic concentration ranges in serum. The measurement of VA serum concentrations using chromatographic methods requires a sample preparation step. In this context, this study aims to describe the development and validation of an assay for VA measurement in serum using a new microextraction strategy, known as BioSPME, followed by GC-MS analysis.

Validation of an analytical method for the simultaneous determination of 16 drugs and metabolites in hair in the context of driving license granting.

The use of psychoactive substances has been associated with increased risk for traffic accidents. Hair testing has become a routine practice in clinical and forensic toxicological laboratories, with a unique perspective in the investigation of drug consumption. The study aimed to develop and validate a UHPLC-MS/MS method for the determination of multiple drugs in hair, to be used for toxicological examination in driving license granting.

Determination of cannabinoids in plasma using salting-out-assisted liquid-liquid extraction followed by LC-MS/MS analysis.

The detection of the markers of Cannabis consumption in biological specimens is an important task for drug testing laboratories in varous contexts. A simple assay combining salting-out assisted liquid-liquid extraction sample preparation and LC-MS/MS analysis was applied to the measurement of Δ -tetrahydrocannabinol, 11-nor-9-carboxy-Δ -tetrahydrocannabinol (THC-COOH), 11-hydroxy-Δ -tetrahydrocannabinol, cannabinol and cannabidiol concentrations in 100 μl plasma specimens. The assay had linearity of 1-100 ng ml for THC-COOH and 0.

Ibuprofen during gestation prevents some changes in physical and reflex development in offspring in a model of hyperleucinemia and maternal inflammation.

Maple Syrup Urine Disease (MSUD) is caused by a severe deficiency in the branched-chain ketoacid dehydrogenase complex activity. Patients MSUD accumulate the branched-chain amino acids leucine (Leu), isoleucine, valine in blood, and other tissues. Leu and/or their branched-chain α-keto acids are linked to neurological damage in MSUD.

Simultaneous Determination of Cocaine and Metabolites in Human Plasma Using Solid Phase Micro-Extraction Fiber Tips C18 and UPLC-MS/MS.

The determination of cocaine (COC) and its metabolites ecgonine methyl ester (EME), benzoylecgonine (BZE), norcocaine (NCOC) and cocaethylene (CE) in human plasma is relevant in clinical and forensic toxicology. An efficient extraction and clean-up of plasma specimens for the simultaneous determination of BZE along with COC and basic metabolites is challenging due to their widely different polarities and ionization characteristics. Recently, biocompatible SPME LC tips C18 became commercially available.

Simultaneous determination of cocaine, ecgonine methyl ester, benzoylecgonine, cocaethylene and norcocaine in dried blood spots by ultra-performance liquid chromatography coupled to tandem mass spectrometry.

Cocaine (COC) is one of the most widely abused drugs in the world and its sensitive and its reliable measurement in blood is of great importance in the field of forensic and clinical toxicology. Additionally, the determination of COC metabolites such as benzoylecgonine (BZE), cocaethylene (CE), ecgonine methyl ester (EME), and norcocaine (NCOC) are also of complementary diagnostic value. The quantification of COC and metabolites in dried blood spots (DBS) may be an alternative to conventional collection methods with several advantages, including easier, on-site, collection, transportation and storage.

Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity.

Background: Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established based on patient's body surface area, an approach associated with large inter-individual variability in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic than IRI.

DPD functional tests in plasma, fresh saliva and dried saliva samples as predictors of 5-fluorouracil exposure and occurrence of drug-related severe toxicity.

Objective: to evaluate plasma and salivary uracil (U) to dihydrouracil (UH2) ratios as tools for predicting 5-fluorouracil systemic exposure and drug-related severe toxicity, and clinically validate the use of dried saliva spots (DSS) as an alternative sampling strategy for dihydropyrimidine dehydrogenase (DPD) deficiency assessment.

Methods: Pre-chemotherapy plasma, fresh saliva and DSS samples were obtained from gastrointestinal patients (N = 40) for measurement of endogenous U and UH2 concentrations by LC-MS/MS. A second plasma sample collected during 5FU infusion was used for 5FU area under the curve (AUC) determination by HPLC-DAD.

Analytical and clinical validation of a dried blood spot assay for the determination of paclitaxel using high-performance liquid chromatography-tandem mass spectrometry.

Background: Paclitaxel (PCT) is a chemotherapeutic drug widely used for the treatment of several types of tumors, and its use is associated with severe adverse events, mainly neurologic and hematopoietic toxicities. The relation between systemic exposure and clinical response to PCT was previously described, making paclitaxel a potential candidate for therapeutic drug monitoring (TDM). The use of dried blood spot (DBS) sampling could allow complex sampling schedules required for TDM of PCT.

Determination of irinotecan and its metabolite SN-38 in dried blood spots using high-performance liquid-chromatography with fluorescence detection.

Irinotecan (IRI) is an antineoplastic drug widely used for the treatment of colorectal and advanced pancreatic cancer. Despite its clinical utility, the clinical use of IRI is associated with potentially severe hematopoietic and gastrointestinal toxicities. The quantification of IRI and its active metabolite SN-38 in dried blood spots (DBS) may be an alternative to individualize the drug dose through a minimally invasive and easy collection method.