Search

Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is a promising tool for adherence monitoring. This study focused on development of an analytical methodology to improve VAMS-based strategies for adherence assessment by analyzing angiotensin-converting-enzyme (ACE) inhibitors, loop diuretics, a potassium-sparing diuretic, and a thiazide diuretic. Development included sample preparation, chromatographic conditions, mass spectrometry settings, validation, and demonstrating proof of concept. Quantification of analytes, by name furosemide, hydrochlorothiazide, lisinopril, torasemide, and the active metabolites, canrenone, enalaprilat, and ramiprilat in finger prick blood (FPB), was validated based on international guidelines. Selectivity, carryover, and within/between-run accuracy and precision were in accordance with the recommendations. The matrix effect was evaluated at three different hematocrit levels (HT: 20%, 40%, 60%) and the coefficients of variation did not exceed 15%. Dilution integrity (1:10 and 1:20) was given for all analytes except lisinopril, yet for lisinopril, the therapeutic range was already covered by the calibration range. Long-term stability in VAMS tips was tested for 2 weeks at 24 °C in the dark and revealed no degradation of analytes. The proof of concept was performed by analyzing 35 intakes of ACE-inhibitors and diuretics in 18 VAMS and matched plasma samples. Hereby, determined concentration in FPB and plasma cannot be used interchangeably, and thus specific reference ranges for whole blood must be established. Nevertheless, the VAMS-based strategy was shown to be suitable for assessing adherence of all classes of antihypertensive drugs used in the guidelines to manage hypertension. Graphical abstract

The active, poisonous constituents in Taxus baccata, the yew plants, are taxine alkaloids whose main action is suggested to be a block of calcium and sodium channels. The main alkaloids are taxine B (30%) and taxine A (1.3%). Symptoms can include bradycardia, bradypnea, diastolic, and cardiac standstill. The current investigation reports the analytical toxicology of human blood and urine to confirm a suspected ingestion of yew needles. This includes the qualitative detection of several yew ingredients, including the main alkaloids, the validated quantification of 3,5-dimethoxyphenol, and the discussion of suitable analytical targets. After analyzing human specimens and yew needle extracts using the developed procedures, the five alkaloids 1-deotaxine B, taxicatin, taxine A, taxine B, and taxine I could be detected and tentatively identified. Finally, taxine A and B can be recommended as analytical targets besides 3,5-dimethoxyphenol.

Chloroquine, a drug approved for the treatment of malaria, is frequently used to commit suicide. We report about a suicide attempt by ingesting a high dose of chloroquine in combination with other drugs. Findings of the emergency toxicology screening of blood and urine and those of the follow-up analyses in blood are discussed. Systematic toxicological analysis approaches revealed the presence of chloroquine, butylscopolamine, cafedrine, diazepam, lorazepam, metoclopramide, nordazepam, norephedrine and 11-nor-9-carboxy-∆9-tetrahydroxycannabinol in blood and/or urine of the subject. Suicide due to a combination of chloroquine and benzodiazepines is known as the so-called “Kusch method” in German-speaking countries. The initial chloroquine plasma concentration was determined to be 9.6 mg/L after precipitation and analysis by liquid chromatography–high-resolution tandem mass spectrometry. The analytical procedure was developed ad hoc and validated in accordance with international recommendations. Clinical toxicological follow-up analyses in blood were performed over a period of 3 weeks. The chloroquine concentration remained above the therapeutic range (up to 0.5 mg/L) for 2 weeks and dropped to 0.3 mg/L after 3 weeks. Furthermore, monodesethylchloroquine (MDCQ) and bisdesethylchloroquine (BDCQ) were determined to be the most abundant metabolites in plasma. Within 3 weeks, the area ratios of MDCQ and chloroquine increased 4-fold (from 0.090 to 0.350), and those of BDCQ and chloroquine increased 100-fold (from 0.002 to 0.218). This information may help to estimate the chloroquine excretion progress in the future.

Every year, more new psychoactive substances (NPSs) emerge in the market of the drugs of abuse. NPSs belong to various chemical classes, such as synthetic cannabinoids, phenethylamines, opioids, and benzodiazepines. The detection of NPSs intake using different types of biological matrices is challenging for clinical toxicologists because of their structural diversity and the lack of information on their toxicokinetics, including their metabolic fate.PubMed-listed articles reporting mass spectrometry-based bioanalytical approaches for NPSs detection published during the past 5 years were identified and discussed. Furthermore, the pros and cons of using common biological matrices in clinical toxicology (CT) settings to screen for NPSs are highlighted in this review article.Twenty-six articles presenting multianalyte screening methods for use in the field of CT were considered. The advantages and disadvantages of different biological matrices are discussed with a particular view of the different analytical tasks in CT, especially emergency toxicology. Finally, an outlook introduces the emerging trends in biosamples used in CT, such as the exhaled breath.Blood and urine represent the most common biological matrices used in a CT setting; however, reports concerning NPSs detection in alternative matrices are also available. Noteworthy, the selection of the biological matrix must depend on the clinician's enquiry because the individual advantages and disadvantages must be considered.

Volumetric absorptive microsampling (VAMS), an emerging microsampling technique, is expected to overcome some disadvantages of dried blood spots. This study aimed to develop and evaluate a VAMS-based strategy for quantifying ten frequently prescribed antihypertensive drugs (AHD) (amlodipine, bisoprolol, candesartan, carvedilol, lercanidipine, losartan carboxylic acid, metoprolol, nebivolol, telmisartan, valsartan) in finger prick blood (FPB) within the scope of adherence monitoring. The straightforward workflow consisted of VAMS tip hydration and subsequent precipitation. Samples were analyzed by using reversed phase ultra-high performance liquid chromatography coupled to orbitrap mass spectrometry operating in parallel reaction monitoring mode. The analytical procedure was successfully validated based on international recommendations for most of the analytes. Selectivity and within/between-run accuracy and precision were in accordance with the recommendations. Internal standard normalized matrix factor met recommended criteria for all analytes at HT 20%, 40%, and 60% except for amlodipine were the CV exceeded 15% at HT 20% (CV 18%). Dilution integrity was given for all substances, covering the quantification in the upper part of the therapeutic range of selected AHD. Long-term stability in VAMS tips was tested and revealed degradation of lercanidipine after one week of storage at 24 °C. A proof of concept of the analytical applicability was done by quantification of selected AHD in VAMS tips and matched plasma samples. Results revealed that determined concentration in FPB by VAMS and plasma cannot be used interchangeably, and thus that specific reference ranges have to be established. However, a novel VAMS application was implemented in the context of adherence monitoring for at least the investigated AHD.

Nonadherence to antihypertensive drugs therapy is known to be a serious issue in hypertension treatment. Liquid chromatography (LC) coupled to mass spectrometry (MS) was shown to allow the assessment of such nonadherence in blood and urine sample. However, their sampling may represent a logistical challenge and are often not favored by the patients. We questioned whether oral fluid (OF) might be an easier accessible alternative matrix for adherence monitoring of cardiovascular drugs (CD). A qualitative method for adherence monitoring of 78 commonly prescribed cardiovascular drugs in OF using LC high-resolution MS (LC-HRMS/MS) was therefore developed, validated, and used to study the presence of antihypertensive medication in OF. Selectivity, ion suppression and enhancement due coeluting analytes, carry over, limits of detection (LOD), limits of identification (LOI), recovery (RE), matrix effects (ME), and process efficiency (PE) were investigated. For demonstrating applicability, over 50 OF samples were investigated and data were compared to findings in blood and urine. Selectivity in OF was given for all compounds via their MS2 spectra and no total suppression of signals could be observed. Determined LOI in OF for ten analytes was higher than the given therapeutic plasma concentration. Furthermore, RE, ME, and PE were in acceptable ranges for more than 65% of the compounds. In total, 208 prescriptions of CD to 57 patients were analyzed and demonstrated the suitability of for adherence monitoring in principle. OF was comparable to plasma regarding the drug categories and the frequencies of hits, except for acidic compounds but more hits could be found in urine samples. A analytical method using OF as analytical matrix was successfully developed. Application showed that it might be a suitable alternative for adherence monitoring of selected drugs in the future, particularly those having no acidic function.