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Pharmaceuticals
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Analytical Techniques in the Pharmaceutical Sciences 2023
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Analytical Techniques in the Pharmaceutical Sciences 2023

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 8418

Special Issue Editors

Dr. Luisa Barreiros

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Guest Editor
LAQV, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
Interests: separation techniques; mass spectrometry; sample preparation; complex matrices; analytical and bioanalytical methods
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marcela Segundo

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Guest Editor
LAQV/REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, R Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Interests: high-throughput analysis; trace analysis of organics; automation; water analysis; pharmaceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of analytical techniques is extremely relevant to the pharmaceutical area, being required for a myriad of applications that comprise the identification and quantification of drug substances in pharmaceutical ingredients, pharmaceutical formulations, and biological matrices. During the process of drug development, the assessment of the pharmacokinetics and pharmacodynamics of each target drug is crucial to define optimum dose and administration schedules. Moreover, therapeutic drug monitoring involving the measurement of drug concentrations in plasma, serum, or blood is increasingly being applied to monitor patient treatment compliance. In recent years, the quantification of active compounds in drug delivery systems, in particular the determination of nanoparticles carrying drugs in biological samples, has emerged as a hot topic. Furthermore, the rising number of biopharmaceuticals and biosimilars demands the establishment of new methodologies for their characterization and quality control.

Many analytical methods have been developed over the years to detect and measure pharmaceutical compounds in different matrices and at different stages of the drug development process. Taking into account the complexity of real matrices and that target pharmaceutical compounds may be present at trace levels, the development of accurate and reliable techniques for their determination is still a challenge. Sample treatment procedures are generally necessary for analyte extraction, preconcentration, and clean-up, followed by instrumentally or biologically based techniques for analytical determination.

This Special Issue is dedicated to the most recent advances in the analytical determination of pharmaceutical compounds. We invite authors to submit review or original research articles on this topic, including the development of novel analytical and bioanalytical strategies based on state-of-the-art techniques, such as chromatography with mass spectrometry detection, and also innovative alternative methods toward a fast, simple, sustainable, and cost-efficient analysis of pharmaceuticals.

Dr. Luisa Barreiros
Prof. Dr. Marcela Segundo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • drug substances
  • pharmaceuticals
  • biopharmaceuticals
  • biosimilars
  • nanoparticles
  • biological matrices
  • sample preparation
  • separation techniques
  • mass spectrometry
  • screening methods
  • sensors

Related Special Issue

Published Papers (7 papers)

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Research

14 pages, 825 KiB  
Article
A New and Rapid LC-MS/MS Method for the Determination of Cysteamine Plasma Levels in Cystinosis Patients
by Raffaele Simeoli, Sara Cairoli, Marcella Greco, Francesco Bellomo, Alessandro Mancini, Chiara Rossi, Carlo Dionisi Vici, Francesco Emma and Bianca Maria Goffredo
Pharmaceuticals 2024, 17(5), 649; https://doi.org/10.3390/ph17050649 - 16 May 2024
Viewed by 442
Abstract
Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved [...] Read more.
Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)’s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5–26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50–3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60–36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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11 pages, 4974 KiB  
Article
Analyzing Alkyl Bromide Genotoxic Impurities in Febuxostat Based on Static Headspace Sampling and GC-ECD
by Alexandros Kavrentzos, Elli Vastardi, Evangelos Karavas, Paraskevas D. Tzanavaras and Constantinos K. Zacharis
Pharmaceuticals 2024, 17(4), 422; https://doi.org/10.3390/ph17040422 - 26 Mar 2024
Viewed by 649
Abstract
Herein, a sensitive and selective gas chromatography-electron capture detector (GC-ECD) method was developed and validated for the quantification of trace levels of five bromo-containing genotoxic impurities in Febuxostat active pharmaceutical ingredient (API) after headspace sampling (HS). Multivariate experimental designs for the optimization of [...] Read more.
Herein, a sensitive and selective gas chromatography-electron capture detector (GC-ECD) method was developed and validated for the quantification of trace levels of five bromo-containing genotoxic impurities in Febuxostat active pharmaceutical ingredient (API) after headspace sampling (HS). Multivariate experimental designs for the optimization of static headspace parameters were conducted in two stages using fractional factorial design (FFD) and central composite design (CCD). The optimum headspace conditions were 5 min of extraction time and a 120 °C extraction temperature. Baseline separation on the analytes against halogenated solvents was carried out using an Agilent DB-624 (30 m × 0.32 mm I.D., 1.8 μm film thickness) stationary phase under isothermal conditions. The method was validated according to ICH guidelines in terms of specificity, linearity, the limits of detection and quantification, precision and accuracy. The linearity was assessed in the range of 5–150% with respect to the specification limit. The achieved LOD and LOQ values ranged between 0.003 and 0.009 and 0.01 and 0.03 μg mL−1, respectively. The accuracy of the method (expressed as relative recovery) was in the range of 81.5–118.2%, while the precision (repeatability, inter-day) was less than 9.9% in all cases. The validated analytical protocol has been successfully applied to the determination of the impurities in various Febuxostat API batch samples. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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15 pages, 2208 KiB  
Article
Greener and Whiter Analytical Chemistry Using Cyrene as a More Sustainable and Eco-Friendlier Mobile Phase Constituent in Chromatography
by Sami El Deeb, Khalid Abdelsamad and Maria Kristina Parr
Pharmaceuticals 2023, 16(10), 1488; https://doi.org/10.3390/ph16101488 - 19 Oct 2023
Viewed by 1611
Abstract
Cyrene (dihydrolevoglucosenone) was evaluated for the first time as a potential sustainable mobile phase solvent in reversed-phase chromatography. As a benign biodegradable solvent, Cyrene is an attractive replacement to classical non-green organic chromatographic solvents such as acetonitrile and a modifier, co-eluent to known [...] Read more.
Cyrene (dihydrolevoglucosenone) was evaluated for the first time as a potential sustainable mobile phase solvent in reversed-phase chromatography. As a benign biodegradable solvent, Cyrene is an attractive replacement to classical non-green organic chromatographic solvents such as acetonitrile and a modifier, co-eluent to known green solvents such as ethanol. Compared to ethanol, Cyrene is less toxic, non-flammable, biobased, biodegradable, and a cheaper solvent. A fire safety spider chart was generated to compare the properties of Cyrene to ethanol and show its superiority as a greener solvent. Cyrene’s behavior, advantages, and drawbacks in reversed-phase chromatography, including the cut-off value of 350 nm, elution power, selectivity, and effect on the column, were investigated using a model drug mixture of moxifloxacin and metronidazole. A monolithic C18 (100 × 4.6 mm) column was used as a stationary phase. Different ratios of Cyrene: ethanol with an aqueous portion of sodium acetate buffer mobile phases were tested. A mobile phase consisting of Cyrene: ethanol: 0.1 M sodium acetate buffer pH 4.25 (8:13:79, v/v/v) was selected as the most suitable mobile phase system for separating and simultaneously determining metronidazole and moxifloxacin. The greenness and whiteness of the method were evaluated using the qualitative green assessment tool AGREE and the white analytical chemistry assessment tool RGB12. Further potentials of Cyrene as a solvent or modifier in normal phase chromatography, liquid chromatography–mass spectrometry, and supercritical fluid chromatography are discussed. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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13 pages, 1997 KiB  
Article
Expanding the Analytical Toolbox: Developing New Lys-C Peptide Mapping Methods with Minimized Assay-Induced Artifacts to Fully Characterize Antibodies
by Y. Diana Liu, Michelle Irwin Beardsley and Feng Yang
Pharmaceuticals 2023, 16(9), 1327; https://doi.org/10.3390/ph16091327 - 20 Sep 2023
Viewed by 1503
Abstract
Peptide mapping is an important tool used to confirm that the correct sequence has been expressed for a protein and to evaluate protein post-translational modifications (PTMs) that may arise during the production, processing, or storage of protein drugs. Our new orally administered drug [...] Read more.
Peptide mapping is an important tool used to confirm that the correct sequence has been expressed for a protein and to evaluate protein post-translational modifications (PTMs) that may arise during the production, processing, or storage of protein drugs. Our new orally administered drug (Ab-1), a single-domain antibody, is highly stable and resistant to proteolysis. Analysis via the commonly used tryptic mapping method did not generate sufficient sequence coverage. Alternative methods were needed to study the Ab-1 drug substance (75 mg/mL) and drug product (3 mg/mL). To meet these analytical needs, we developed two new peptide mapping methods using lysyl endopeptidase (Lys-C) digestion. These newly developed protein digestion protocols do not require desalting/buffer-exchange steps, thereby reducing sample preparation time and improving method robustness. Additionally, the protein digestion is performed under neutral pH with methionine acting as a scavenger to minimize artifacts, such as deamidation and oxidation, which are induced during sample preparation. Further, the method for low-concentration samples performs comparably to the method for high-concentration samples. Both methods provide 100% sequence coverage for Ab-1, and, therefore, enable comprehensive characterization for its product quality attribute (PQA) assessment. Both methods can be used to study other antibody formats. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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16 pages, 2337 KiB  
Article
Development of Novel Micellar-Enhanced High-Throughput Microwell Spectrofluorimetric Method for Quantification of Lorlatinib: Application to In Vitro Drug Release and Analysis of Urine Samples
by Abdullah M. Al-Hossaini, Hany W. Darwish, Ahmed H. Bakheit and Ibrahim A. Darwish
Pharmaceuticals 2023, 16(9), 1260; https://doi.org/10.3390/ph16091260 - 6 Sep 2023
Viewed by 921
Abstract
Lorlatinib (LOR) is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor drug. The Food and Drug Administration (FDA) has granted an approval for the use of LOR as a first therapeutic intervention for individuals diagnosed with ALK-positive metastatic and advanced non-small-cell lung [...] Read more.
Lorlatinib (LOR) is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor drug. The Food and Drug Administration (FDA) has granted an approval for the use of LOR as a first therapeutic intervention for individuals diagnosed with ALK-positive metastatic and advanced non-small-cell lung cancer (NSCLC). The present study outlines, for the first time, the development and validation of an innovative microwell-based spectrofluorimetric (MW-SFL) method for the quantification of LOR. The proposed method involved the enhancement of the weak native fluorescence of LOR by its micellization into the sodium lauryl sulfate (SLS) micelles. The procedures of the method were conducted in white opaque plates with 96 microwells, and the enhanced fluorescence signals were measured by a fluorescence plate reader at 405 nm after excitation at 310 nm. The measured relative fluorescence intensity (RFI) had a linear relationship with LOR concentrations in the range of 60–1600 ng mL−1. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be 19 and 56 ng mL−1, respectively. The method’s accuracy and precision were assessed using a recovery study; the recovery values ranged from 99.98% to 101.40%, accompanied by relative standard deviation (RSD) values of 0.42% to 1.59%. The proposed MW-SFL method combined the advantages of the intrinsically high sensitivity of the spectrofluorimetric measurement and the excellent throughput of the microwell-based approach. The results proved the method is effective in the determination of LOR in its pharmaceutical tablets, tablet dissolution testing, as well as in spiked urine with a high degree of precision and accuracy. The MW-SFL method is notable for its simple procedures and utilization of water as a solvent, as well as minimal quantities of sample solutions. These features align with its ecofriendly approach to green chemistry principles. These advantages gave the proposed MW-SFL method a high potential value for the determination of LOR in clinical and quality control laboratories. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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13 pages, 3675 KiB  
Article
Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats
by Xiaochen Niu, Dan Chen, Wei He, Yu Tang and Jianchun Zhao
Pharmaceuticals 2023, 16(8), 1153; https://doi.org/10.3390/ph16081153 - 14 Aug 2023
Viewed by 1037
Abstract
Plinabulin, a new antitumor drug developed from marine natural products that targets microtubules in cancer cells, is currently being tested in a phase III clinical study. Plinabulin has been clinically proven to be effective on leukopenia. However, to our knowledge, there are no [...] Read more.
Plinabulin, a new antitumor drug developed from marine natural products that targets microtubules in cancer cells, is currently being tested in a phase III clinical study. Plinabulin has been clinically proven to be effective on leukopenia. However, to our knowledge, there are no reports investigating the pharmacokinetics of plinabulin in individuals with leukopenia and healthy individuals. In this study, we developed a rapid and sensitive UHPLC-MS/MS method for the detection of plinabulin for the first time. Using a novel cyclophosphamide-induced leukopenia model, we investigated the differences in the pharmacokinetic characteristics of plinabulin between rats with leukopenia and normal rats. Plinabulin and propranolol (IS) peaks were separated by gradient elution for a total run time of 5 min. The methodological validation showed a good accuracy (101.96–109.42%) and precision (RSD ≤ 5.37%) with the lower limit of quantification at 0.5 ng/mL. The recovery of plinabulin was between 91.99% and 109.75% (RSD ≤ 7.92%). The values of the area under the plasma concentration-time curve (AUC0-t) for leukopenia groups and control groups at doses of 0.5 mg/kg, 1 mg/kg, and 3 mg/kg were 148.89 ± 78.74 h·μg/L and 121.75 ± 31.56 h·μg/L; 318.15 ± 40.00 h·μg/L and 272.06 ± 42.85 h·μg/L; and 1432.43 ± 197.47 h·μg/L and 1337.12 ± 193.56 h·μg/L; respectively. The half-lives (t1/2s) of plinabulin were 0.49–0.72 h for leukopenia groups and 0.39–0.70 h for control groups at three doses, and the clearance rates (CLs) of plinabulin were 2.13–3.87 L/h/kg for leukopenia groups and 2.29–4.23 L/h/kg for control groups. Pharmacokinetic results showed that there was no significant pharmacokinetic difference between the normal group and the leukopenia group. Based on the power model, plinabulin exhibits a lack of dose proportionality over the dose range of 0.5–3 mg/kg after intravenous administration. This study provides guidance for the development of plinabulin as a potential candidate for the treatment of chemotherapy-induced leukopenia. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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17 pages, 2508 KiB  
Article
Application of the Analytical Procedure Lifecycle Concept to a Quantitative 1H NMR Method for Total Dammarane-Type Saponins
by Wenzhu Li, Jiayu Yang, Fang Zhao, Xinyuan Xie, Jianyang Pan and Haibin Qu
Pharmaceuticals 2023, 16(7), 947; https://doi.org/10.3390/ph16070947 - 29 Jun 2023
Viewed by 1105
Abstract
Dammarane-type saponins (DTSs) exist in various medicinal plants, which are a class of active ingredients with effects on improving myocardial ischemia and immunomodulation. In this study, a quantitative 1H NMR method of total DTSs in herbal medicines was developed based on the [...] Read more.
Dammarane-type saponins (DTSs) exist in various medicinal plants, which are a class of active ingredients with effects on improving myocardial ischemia and immunomodulation. In this study, a quantitative 1H NMR method of total DTSs in herbal medicines was developed based on the analytical procedure lifecycle. In the first stage (analytical procedure design), the Ishikawa diagram and failure mode effects and criticality analysis were used to conduct risk identification and risk ranking. Plackett–Burman design and central composite design were used to screen and optimize critical analytical procedure parameter. Then, the method operable design region was obtained through modeling. In the second stage (analytical procedure performance qualification), the performance of methodological indexes was investigated based on analytical quality by design. As examples of continued procedure performance verification, the method was successfully applied to determine the total DTSs in herbal pharmaceutical preparations and botanical extracts. As a general analytical method to quantify total DTSs in medicinal plants or pharmaceutical preparations, the developed method provides a new quality control strategy for various products containing dammarane-type saponin. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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