Applications of Liquid Chromatography Coupled with Mass Spectrometry (LC-MS/MS) in Drug Analysis

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 1 July 2024 | Viewed by 5143

Special Issue Editors


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Guest Editor
National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
Interests: Bioanalysis; liquid chromatography; mass spectrometry; therapeutic drug monitoring; biomarker profiling; pharmacology

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Guest Editor
Physical and Colloidal Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
Interests: bioanalysis; liquid chromatography; process optimization, biopharmacy, bioavailability enhancement; metabolism, natural product chemistry

Special Issue Information

Dear Colleagues,

The significant and impressive progress in pharmaceutical analysis has been sustained by the continuous development of powerful analytical instrumentation. Nevertheless, due to the permanent and complex demands of this field, pharmaceutical analysis remains challenging. At the forefront is drug development, with its need for new characterization methods, especially those driven by the recent advances in vaccine technology, as well as in formulation of large-molecule-based innovative drug products that are quickly becoming the forerunning therapy option in critical diseases such as cancer, rheumatoid disorders or autoimmune disorders. However, this does not mean that small molecule analysis is losing ground. From impurities and stability determination to adsorption, metabolism and excretion; therapeutic drug monitoring and toxicology; animal healthcare, food control; or the environmental fate of pharmaceuticals, researchers are working tirelessly to achieve more specific, sensitive and suitable methods for drug analysis. Finding potential cellular targets for new or drugs and elucidating their mechanism of action are also important aspects of pharmaceutical analysis. The constant demands of the pharmaceutical field have prompted the steady development of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which remains one of the most important tools in pharmaceutical. This synergy will be reflected in a Special Issue titled “Applications of Liquid Chromatography Coupled With Mass Spectrometry (LC-MS/MS) in Drug Analysis,” published in the journal Pharmaceuticals. I am pleased to invite you to submit communications, research articles or high-quality review papers to this Special Issue.

Dr. Isabela Tarcomnicu
Dr. Valentina Anuta
Guest Editors

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Keywords

  • pharmaceutical analysis
  • bioanalysis
  • liquid chromatography
  • mass spectrometry
  • impurities
  • bioavailability
  • metabolism
  • environmental fate

Published Papers (5 papers)

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Research

16 pages, 2942 KiB  
Article
A Multi-Residue Analytical Method for Assessing the Effects of Stacking Treatment on Antimicrobial and Coccidiostat Degradation in Broiler Litter
by Solomon Efriem, Malka Britzi, Stefan Soback, Chris Sabastian and Sameer J. Mabjeesh
Pharmaceuticals 2024, 17(2), 203; https://doi.org/10.3390/ph17020203 - 04 Feb 2024
Viewed by 746
Abstract
Antimicrobial drugs and coccidiostat compounds are commonly used in poultry farming. These compounds are subsequently excreted and released into the environment via broiler litter (BL) and can re-enter the food chain as fertilizer or animal feed. Such residue in animal feed can encourage [...] Read more.
Antimicrobial drugs and coccidiostat compounds are commonly used in poultry farming. These compounds are subsequently excreted and released into the environment via broiler litter (BL) and can re-enter the food chain as fertilizer or animal feed. Such residue in animal feed can encourage the appearance of antibiotic-resistant bacteria as well as toxicity. Most analytical methods used to identify and quantitate these drug residues are traditional, and are specific to some antimicrobials and present limitations in assessing complex matrixes like BL. The aim of this study was to develop a multi-residue analytic method for assessing 30 antimicrobial drugs and coccidiostats associated with BL. We investigated the presence and the effects of biotic stack treatment on the degradation of drug residue in BL. Liquid-liquid extraction (LLE) and solid phase extraction (SPE) were replaced by Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) clean-up steps and detected by liquid chromatography mass spectrometry (LC/MS/MS). Results show that a wide spectrum of residues were detected from 0.4 to 8.9 mg kg−1. Following lab-scale stacking treatment, tilmicosin and eight coccidiostats persisted in BL (26–100%). This research supports the need for better understanding, regulation, and management of the use of BL that might carry a high risk of residue drugs. Full article
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19 pages, 1743 KiB  
Article
A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study
by Lin-Zhi Chen, David Roos, Elsy Philip, Emily G. Werth, Stephanie Kostuk, Hongbin Yu and Holger Fuchs
Pharmaceuticals 2024, 17(2), 193; https://doi.org/10.3390/ph17020193 - 31 Jan 2024
Cited by 1 | Viewed by 701
Abstract
BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and [...] Read more.
BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and albumin levels in plasma, the vitreous humor, the aqueous humor, and retina tissue at various timepoints post-dose. A comprehensive bioanalytical approach was implemented in support of this study. Five immunocapture-LC-MS/MS assays were developed and qualified for quantitating BI-X in different matrices, while ELISA was used for albumin measurement. Immunocapture at the protein or peptide level was evaluated to achieve adequate assay sensitivity. Drug and albumin assays were applied for the analysis of the monkey study samples. Full article
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0 pages, 1762 KiB  
Article
Paclitaxel and Therapeutic Drug Monitoring with Microsampling in Clinical Practice
by Mirjana Radovanovic, Peter Galettis, Alex Flynn, Jennifer H. Martin and Jennifer J. Schneider
Pharmaceuticals 2024, 17(1), 63; https://doi.org/10.3390/ph17010063 - 29 Dec 2023
Viewed by 911
Abstract
Paclitaxel is an anticancer agent efficacious in various tumors. There is large interindividual variability in drug plasma concentrations resulting in a wide variability in observed toxicity in patients. Studies have shown the time the concentration of paclitaxel exceeds 0.05 µM is a predictive [...] Read more.
Paclitaxel is an anticancer agent efficacious in various tumors. There is large interindividual variability in drug plasma concentrations resulting in a wide variability in observed toxicity in patients. Studies have shown the time the concentration of paclitaxel exceeds 0.05 µM is a predictive parameter of toxicity, making dose individualization potentially useful in reducing the adverse effects. To determine paclitaxel drug concentration, a venous blood sample collected 24 h following the end of infusion is required, often inconvenient for patients. Alternatively, using a microsampling device for self-sampling would facilitate paclitaxel monitoring regardless of the patient’s location. We investigated the feasibility of collecting venous and capillary samples (using a Mitra® device) from cancer patients to determine the paclitaxel concentrations. The relationship between the venous plasma and whole blood and venous and capillary blood (on Mitra®) paclitaxel concentrations, defined by a Passing–Bablok regression, were 0.8433 and 0.8569, respectively. Demonstrating a clinically acceptable relationship between plasma and whole blood paclitaxel concentration would reduce the need to establish new target concentrations in whole blood. However, in this study, comparison of venous and capillary blood using Mitra® for sampling displayed wide confidence intervals suggesting the results from the plasma and whole blood on this device may not be interchangeable. Full article
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14 pages, 2093 KiB  
Article
Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry
by Wenjing Li, Yang Li, Junlong Cai, Yue Wang, Yanan Liu, Hankun Hu and Liang Liu
Pharmaceuticals 2023, 16(11), 1537; https://doi.org/10.3390/ph16111537 - 30 Oct 2023
Viewed by 1239
Abstract
Systemic antifungal agents are essential for high-risk patients undergoing immunosuppressive therapy or cancer chemotherapy because of the rapid increase in opportunistic fungal infections. Therapeutic drug monitoring is crucial to ensuring the efficacy and safety of antifungal agents owing to their pharmacokinetic variability. In [...] Read more.
Systemic antifungal agents are essential for high-risk patients undergoing immunosuppressive therapy or cancer chemotherapy because of the rapid increase in opportunistic fungal infections. Therapeutic drug monitoring is crucial to ensuring the efficacy and safety of antifungal agents owing to their pharmacokinetic variability. In the present study, we developed and validated a quantitative method for the simultaneous detection of seven commonly used antifungal drugs (amphotericin B, isavuconazole, voriconazole, fluconazole, posaconazole, caspofungin, and micafungin) using liquid chromatography-tandem mass spectrometry. Methanol (containing 0.1% formic acid) was used for protein precipitation and only 50 μL of serum was required for the analysis. Chromatographic separation was conducted using a Waters Acquity UPLC C8 column, and one stable isotope-labeled agent and two analogs were used as internal standards. The calibration curves ranged from 0.1 to 50 μg/mL for all agents, and the correlation coefficient (R2) for all calibration curves was above 0.9835. The intra-day precision (1.2–11.2%), inter-day precision (2.4–13.2%), and mean bias values (−10.9 to 13.6%) were within an acceptable range of ±15%. Successful implementation of the developed method in clinical practice would facilitate the effective monitoring of these antifungal agents. Full article
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14 pages, 2371 KiB  
Article
Early Events after Herpes Simplex Virus-Type 1 Entry Are Necessary for the Release of Gamma-Hydroxybutyrate upon Acute Infection
by Faith O. Osinaga, Yu-Chih Chen, Madan K. Kharel, Yan Waguespack, Sichu Li and Shaochung Victor Hsia
Pharmaceuticals 2023, 16(8), 1104; https://doi.org/10.3390/ph16081104 - 04 Aug 2023
Viewed by 907
Abstract
We reported that gamma-hydroxybutyrate (GHB) is released upon Herpes Simplex Virus Type-1 (HSV-1) acute infection. However, the cellular biochemical processes involved in the production of GHB in infected cells are unclear. This study aims to shed light on the biochemical pathway and the [...] Read more.
We reported that gamma-hydroxybutyrate (GHB) is released upon Herpes Simplex Virus Type-1 (HSV-1) acute infection. However, the cellular biochemical processes involved in the production of GHB in infected cells are unclear. This study aims to shed light on the biochemical pathway and the stage within the viral life cycle responsible for the release of GHB in infected cells. UV-inactivation, acyclovir (ACV), and cycloheximide (CHX) treatments were used to inhibit HSV-1 replication at various stages. Vero cells treated with UV-inactivated HSV-1 significantly decreased GHB production. However, ACV or CHX treatments did not affect GHB production. We also showed that inhibition of glycolytic enzyme enolase by sodium fluoride (NaF) significantly reduces GHB production upon infection. This finding suggests that suppression of glycolytic activity negatively affects cellular GHB production. Our data also indicated that succinic semialdehyde dehydrogenase, an enzyme involved in the shunt of the tricarboxylic acid (TCA) cycle to generate succinic acid, was decreased upon infection, suggesting that infection may trigger the accumulation of succinic semialdehyde, causing the production of GHB. Although the precise mechanism has yet to be defined, our results suggest that early events following infection modulates the release of GHB, which is generated through the metabolic pathways of glycolysis and TCA cycle. Full article
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