Stability of 10 Beta-Lactam Antibiotics in Human Plasma at Different Storage Conditions.

Background: Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in human plasma samples. Beta-lactams are considered unstable, leading to extra challenges in quantification. Therefore, to ensure sample stability and minimize sample degradation before analysis, stability studies are crucial.

Monitoring antihypertensive drug concentrations to determine nonadherence in hypertensive patients with or without a kidney transplant.

Background: Nonadherence to antihypertensive drugs (AHDs) is a major contributor to pseudo-resistant hypertension. The primary objective of this study was to determine the prevalence of nonadherence to AHDs among patients visiting the nephrology and vascular outpatient clinics.

Methods: Patients were eligible to participate in this prospective observational study if they used at least two AHDs that could be measured with a validated UHPLC-MS/MS method and had an office blood pressure at least 140 and/or at least 90 mmHg.

Barriers and facilitators for therapeutic drug monitoring of beta-lactams and ciprofloxacin in the ICU: a nationwide cross-sectional study.

Background: Recent studies demonstrated that failure of achieving pharmacodynamic targets of commonly used antibiotics is common in critically ill patients. Therapeutic drug monitoring (TDM) can contribute to optimize the exposure of beta-lactams and ciprofloxacin. While evidence for TDM of these antibiotics is growing, translation into clinical implementation remains limited.

High-throughput analysis for the simultaneous quantification of nine beta-lactam antibiotics in human plasma by UPC-MS/MS: Method development, validation, and clinical application.

Quantification of beta-lactam antibiotics can be performed by using liquid chromatography in combination with tandem mass spectrometry (MS/MS) or ultraviolet (UV) detection. Since beta-lactam antibiotics are known as highly polar analytes, using standard reversed phase chromatography will result in very early elution, which is often not desirable. Some retention is preferred to reduce matrix effects, because a high amount of non-retained molecular matrix species elute early from the column.

Evaluation of the importance of mixing during preparation of antibiotic infusions.

Background: The mixing step after medication addition to the infusion bag is frequently omitted during the preparation of drug infusions. However, the importance of mixing when preparing antibiotic infusions is still unknown.

Methods: The primary aim of this study was to assess the importance of the mixing step by comparing the concentrations of unmixed antibiotic infusions (cefuroxime, flucloxacillin, meropenem, and vancomycin) with the declared concentration at regular intervals during infusion.

Development and Validation of a Dried Blood Spot Assay Using UHPLC-MS/MS to Identify and Quantify 12 Antihypertensive Drugs and 4 Active Metabolites: Clinical Needs and Analytical Limitations.

Purpose: As nonadherence to antihypertensive drugs (AHDs) can increase the risk of cardiovascular events, hospitalization, and higher costs, there is a need for a reliable, objective, and easy method to assess nonadherence in patients. The dried blood spot (DBS) sampling method used to measure drug concentrations meets these requirements. For detecting nonadherence, identification is more important than quantification.

Clinical Pharmacokinetics of Fosfomycin after Continuous Infusion Compared with Intermittent Infusion: a Randomized Crossover Study in Healthy Volunteers.

Continuous infusion (CON) of fosfomycin has been proposed as potentially advantageous in certain clinical scenarios. However, no clinical data on the pharmacokinetics (PK) of fosfomycin after CON are available to date. This study aimed to investigate the PK of fosfomycin after CON and compare it with intermittent infusion (INT) of fosfomycin.

Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT).

Background: Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1-4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses.

Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.

Background: Pipamperone is a frequently prescribed antipsychotic in children and adolescents in the Netherlands, Belgium, and Germany. However, pediatric pharmacokinetics and the relationship with side effects and efficacy are unknown. Currently, divergent pediatric dosing recommendations exist.

Simultaneous quantification of ambrisentan, macitentan and sitaxentan in human plasma using UPLC-MS/MS.

Endothelin receptor antagonists (ERAs) such as, ambrisentan, macitentan and sitaxentan are primarily used for the treatment of pulmonary arterial hypertension. Considering the rise in endothelin in pre-eclampsia, ERAs may also be useful in its treatment. To evaluate the pharmacokinetics of ERAs, a rapid ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated to determine the concentration of ambrisentan, macitentan and sitaxentan in human plasma.

Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites.

Background: Drug nonadherence is one of the major challenges faced by resistant hypertension patients, and identification of this problem is needed for optimizing pharmacotherapy. Dried blood spot (DBS) sampling is a minimally invasive method designed to detect and determine the degree of nonadherence. In this study, a DBS method for qualifying 8 antihypertensive drugs (AHDs) and 4 active metabolites was developed and validated using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

Drug nonadherence is a common but often overlooked cause of hypertensive urgency and emergency at the emergency department.

Objectives: Over 70% of patients who visit the emergency department with a hypertensive emergency or a hypertensive urgency have previously been diagnosed with hypertension. Drug nonadherence is assumed to play an important role in development of hypertensive urgency and hypertensive emergency, but exact numbers are lacking. We aimed to retrospectively compare characteristics of patients with hypertensive urgency and hypertensive emergency and to prospectively quantify the attribution of drug nonadherence.

Highly sensitive and rapid determination of tacrolimus in peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry.

After solid organ transplantation, tacrolimus is given to prevent rejection. Therapeutic drug monitoring is used to reach target concentrations of tacrolimus in whole blood. Because the site of action of tacrolimus is the lymphocyte, and tacrolimus binds ~80% to erythrocytes, the intracellular tacrolimus concentration in lymphocytes is possibly more relevant.

CYP3A5 and ABCB1 polymorphisms in living donors do not impact clinical outcome after kidney transplantation.

Aim: To investigate the association between donor CYP3A5 and ABCB1 polymorphisms and tacrolimus (Tac)-induced nephrotoxicity and renal function in kidney transplant recipients.

Methods: The CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms were determined in 237 recipients and donors.

Results: There was no significant association between Tac-related nephrotoxicity and donor CYP3A5 and ABCB1 genotype.

Potentially clinically relevant concentrations of Cefazolin, Midazolam, Propofol, and Sufentanil in auto-transfused blood in congenital cardiac surgery.

Background: Use of donor blood in congenital cardiac surgery increases the risk for post-operative morbidity and mortality. To reduce the need for allogenic blood transfusion a technique for peri-operative mechanical red cell salvage is applied. Blood from the operation site is collected in a reservoir, processed, passed through a lipophilic filter and returned to the patient.

Therapeutic Drug Monitoring to Assess Drug Adherence in Assumed Resistant Hypertension: A Comparison With Directly Observed Therapy in 3 Nonadherent Patients.

Resistant hypertension is a common health problem leading to suboptimal cardiovascular prevention. A large number of patients with resistant hypertension have poor medication adherence explaining their assumed resistance to therapy. We combined directly observed therapy (DOT) with therapeutic drug monitoring (TDM) in 3 patients at several time points to enable an extensive feedback on blood pressure (BP) and drug levels.

Simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram in plasma using liquid chromatography-tandem mass spectrometry.

A simple and specific UPLC-MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active metabolite keto-doxapram. The internal standard was fentanyl-d5 for all analytes. Chromatographic separation was achieved with a reversed-phase Acquity UPLC HSS T3 column with a run-time of only 5.

Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Antipsychotics: Drawbacks of Its Clinical Application.

Background: Dried blood spot (DBS) sampling offers a minimally invasive sampling method for therapeutic drug monitoring of antipsychotics. To facilitate implementation in clinical practice, the aim of this study was to perform a clinical validation study of a DBS method for quantification of risperidone, aripiprazole, pipamperone, and their major metabolites 9-OH risperidone and dehydro-aripiprazole in a real-life, clinical setting.

Methods: Paired DBS and venous plasma samples were analyzed (n = 35 for risperidone, n = 21 for aripiprazole, n = 21 for pipamperone).

Quantification of Phosphatidylethanols in Whole Blood as a Proxy for Chronic Alcohol Consumption, Using Ultra Performance Convergence Chromatography Tandem Mass Spectrometry.

Background: Detection of alcohol consumption after a longer period can be useful in certain patient groups. To monitor chronic alcohol consumption, a novel analytical method for the quantification of phosphatidylethanols (PEths) was developed and validated using ultra performance convergence chromatography-tandem mass spectrometry.

Methods: The main phosphatidylethanols like palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol (POPEth), 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphoethanol, and 1,2-dioleoyl-sn-glycero-3-phosphoethanol were analyzed using a simple and fast sample preparation protocol followed by chromatographic separation using ultra performance convergence chromatography, a novel kind of supercritical fluid chromatography.

A fast and sensitive LC-MS/MS method for the quantification of fosfomycin in human urine and plasma using one sample preparation method and HILIC chromatography.

Fosfomycin is an old antibiotic that is increasingly prescribed because of emergence of the antibiotic resistance and the growing incidence of multi-drug resistant infections. Surprisingly, little is known about its pharmacokinetics (PK) and the pharmacodynamics (PD). Quantification of fosfomycin in both urine and plasma provides insight into the PK/PD characteristics of fosfomycin, which is crucial for the optimization of the therapy and the prevention of the emergence of resistance.

High-throughput quantification of 8 antihypertensive drugs and active metabolites in human plasma using UPLC-MS/MS.

Background: To assess drug adherence of patients with hypertension, an analytical method was developed and validated using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The method includes eight frequently prescribed antihypertensive drugs from four classes and their active metabolites: angiotensin converting enzyme inhibitors enalapril and perindopril (active metabolites respectively enalaprilate and perindoprilate), angiotensin II receptor blockers losartan (with the active metabolite losartan carboxylic acid) and valsartan, calcium channel blockers amlodipine and nifedipine and diuretics hydrochlorothiazide and spironolactone (with the active metabolite canrenone).

Methods: The antihypertensive drugs were analyzed using a simple and fast sample preparation protocol with protein precipitation followed by chromatographic separation using a gradient elution on a reversed phase column.