Collision energy-breakdown curves - An additional tool to characterize MS/MS methods.

Background: In tandem mass spectrometry, analyte detection is based on collision-induced fragmentation, which is modulated by the collision energy (CE) setting. Variation in CE leads to differential ion yield, and optimization is usually performed empirically as "tuning" during method development. Our aim was to build a method to objectify the impact of collision energy settings on ion yield for individual compounds.

Target Site Pharmacokinetics of Meropenem: Measurement in Human Explanted Lung Tissue by Bronchoalveolar Lavage, Microdialysis, and Homogenized Lung Tissue.

Pneumonia is one of the most common infections in intensive care patients, and it is often treated with beta-lactam antibiotics. Even if therapeutic drug monitoring in blood is available, it is unclear whether sufficient concentrations are reached at the target site: the lung. The present study was initiated to fill this knowledge gap.

An isotope-dilution LC-MS/MS method for the simultaneous quantification of meropenem and its open-ring metabolite in serum.

Background: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics and, among them, especially meropenem gains importance in the field of laboratory medicine. Meropenem is known to be unstable, resulting in a degradation product with an open beta-lactam ring. For a more comprehensive TDM of meropenem, the aim was to develop a LC-MS/MS method for the simultaneous quantification of meropenem and its main degradation product, the open-ring metabolite (ORM).

Effect of gravimetric correction and type of pipettes used in sample preparation on the precision of LC-MS/MS-based analyses.

Background: Currently, manual pipetting of human sample material is still a key process in sample preparation for chromatographic and mass spectrometric analyses in the clinical laboratory. In most cases, however, pipettes used in clinical laboratories are only specified for handling water-like liquids. Actual pipetted liquid volumes can be verified by weighing within the sample preparation process, and the results can be corrected accordingly (gravimetric correction).

Averaging of results derived from different, simultaneously acquired mass transitions in ID-LC-MS/MS - Potential impact on measurement imprecision.

Background: LC-MS/MS allows for many measurands monitoring different mass transitions simultaneously. So far, such alternative mass transitions are usually assessed as "quantifier and qualifier ions" in order to rule out interferences in individual samples. However, quantification can also be based on assessment of alternative mass transitions for both the measurand and its internal standard, with two distinct results for one injection of an individual sample.

An isotope dilution LC-MS/MS based candidate reference method for the quantification of cyclosporine A, tacrolimus, sirolimus and everolimus in human whole blood.

An isotope dilution LC-MS/MS based candidate reference measurement procedure for the quantification of cyclosporine A, tacrolimus, sirolimus and everolimus in human whole blood is presented to be used for evaluation and standardization of routine assays applied for therapeutic drug monitoring. The assay allows baseline separation of the four immunosuppressive drugs within a total runtime of 9 minutes using a C4 reversed phase column. Sample preparation is based on protein precipitation with zinc sulphate followed by purification with solid phase extraction.

Comparative LC-MS/MS and HPLC-UV Analyses of Meropenem and Piperacillin in Critically Ill Patients.

Background: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics has become a valuable tool to guide dosing in critically ill patients. The main goal of the study was to compare two routinely used techniques for beta-lactam TDM in intensive care unit (ICU) patient samples, namely isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) and high-performance liquid chromatography combined with ultra-violet detection (HPLC-UV).

Methods: A set of 80 sera/plasma samples from ICU patients receiving therapeutic meropenem or piperacillin dosage was investigated.

Isotope dilution LC-orbitrap-HRMS with automated sample preparation for the simultaneous quantification of 11 antimycotics in human serum.

Introduction: The aim of this project was to develop and validate an isotope-dilution liquid chromatography high resolution mass spectrometry (LC-HRMS) method for the quantification of the 11 most widely used systemic antimycotics and to study whether HRMS is a feasible alternative for therapeutic drug monitoring (TDM) when compared to tandem MS (MS/MS) technology.

Methods: After protein precipitation, followed by automated online sample clean-up the analytes were separated within 4 min on a C18 column using an acetonitrile-water gradient. Eleven antimycotics, namely 5-flucytosine, amphotericin B, anidulafungin, fluconazole, isavuconazole, itraconazole, ketoconazole, micafungin, OH-itraconazole, posaconazole and voriconazole were finally quantified in full MS scan mode using positive electrospray ionization (ESI +) with a mass range fromm/z 110-1300 using HRMS.

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses.

There is an ever-increasing demand for the therapeutic drug monitoring of antibiotics in many clinical facilities, particularly with regard to the implementation of hospital antibiotic stewardship programs. In the current work, we present a multiplex high-performance liquid chromatography-tandem mass spectrometry (HPCL-MS/MS) protocol for the quantification of cefepime, meropenem, ciprofloxacin, moxifloxacin, linezolid, and piperacillin, commonly used antibiotics in intensive care units. The method was previously comprehensively validated according to the guideline of the European Medicines Agency.

Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents.

[(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), an organometallic derivative of the irreversible cyclooxygenase-1/2 (COX-1/2) inhibitor acetylsalicylic acid (ASS), demonstrated high growth-inhibitory potential against various tumor cell lines and inhibition of both COX isoenzymes. With the objective of increasing the selectivity for COX-2, we introduced a chlorine substituent in position 3, 4, 5, or 6 of the ASS moiety, respectively. Increased COX-2 selectivity is desirable as this isoenzyme is predominantly related to the development of cancer and abnormal tissue growth.