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Analytical Techniques in Pharmaceutical and Biomedical Analysis

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Analytical Chemistry".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 54839

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Guest Editor
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland
Interests: bioanalysis of drugs; metabolites and endogenous compounds using different analytical techniques, especially HPLC; pharmacokinetics; clinical pharmacokinetics; bioavailability and bioequivalence study
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Guest Editor
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka Str., 60-806 Poznań, Poland
Interests: bioanalysis; HPLC-MS/MS technique; method validation; pharmacokinetics; pharmacogenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development and validation of new analytical and bioanalytical methods play a critical role in drug discovery and therapeutic drug monitoring. The most common challenges that arise during method development are the use of an appropriate sample pretreatment technique for isolating a substance from the matrix and the choice of analytical method for the separation and final determination of the target compounds on the basis of their physicochemical properties.
Therefore, it is our pleasure to invite authors and members of their research groups to submit an article for a Special Issue of Molecules titled Analytical Techniques in Pharmaceutical and Biomedical Analysis, for which we serve as Guest Editors. This Special Issue aims to cover research trends in the development of analytical and bioanalytical methods that are relevant to the isolation, identification, and determination of substances in biomedical and pharmaceutical matrices. Original research papers and reviews on interesting developments related to sample preparation, separation techniques, and spectroscopic methods, as well as any novel techniques for small molecules, peptides, monoclonal antibodies, aptamers, etc., are very welcome.
The submission deadline is 31 July 2021, but we strongly encourage authors to respond to confirm their contributions with their proposed titles by 31 January 2021.
All manuscripts will undergo comprehensive review according to standard journal procedures and policies.

Thank you for considering our invitation.

Dr. Franciszek Główka
Dr. Marta Karaźniewicz-Łada
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • Bioanalysis
  • Biopharmaceutics
  • HPLC
  • GC
  • Electrophoresis
  • Mass spectrometry
  • Pharmacokinetics
  • Pharmaceutical analysis
  • Pharmaceutical formulation
  • Plant materials
  • Spectroscopy
  • Validation

Published Papers (20 papers)

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Research

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9 pages, 1340 KiB  
Article
Quantification and Validation of an HPLC Method for Low Concentrations of Apigenin-7-O-Glucuronide in Agrimonia pilosa Aqueous Ethanol Extract Topical Cream by Liquid–Liquid Extraction
by Jin Seok Lee, Yu Ran Nam, Hyun Jong Kim and Woo Kyung Kim
Molecules 2023, 28(2), 713; https://doi.org/10.3390/molecules28020713 - 11 Jan 2023
Cited by 2 | Viewed by 1818
Abstract
In this study, we aimed to develop and validate a pretreatment method for separating and analyzing the small amounts of biomarkers contained in topical cream formulations. Analyzing semisolid formulations that contain low concentrations of active ingredients is difficult. Cream formulations containing an aqueous [...] Read more.
In this study, we aimed to develop and validate a pretreatment method for separating and analyzing the small amounts of biomarkers contained in topical cream formulations. Analyzing semisolid formulations that contain low concentrations of active ingredients is difficult. Cream formulations containing an aqueous ethanol extract of 0.1% Agrimonia pilosa is an example. Approximately 0.0013% of apigenin-7-O-glucuronide(A7OG) was contained as a biomarker in the cream. To determine the A7OG content present in the cream formulation, liquid–liquid extraction using dichlormethane was applied. In addition, the volume of the distribution liquid was measured using the peak ratios of the indicator component, A7OG, and an internal standard, baicalin. Subsequently, the A7OG content in the cream formulation was calculated. Using this time-saving method, A7OG can be simply analyzed without additional pretreatment steps, such as evaporation and reconstitution. Moreover, the validation results confirmed that this analytical method met all of the criteria. Consequently, A7OG was successfully isolated from the cream, analyzed, and quantified using the developed method. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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16 pages, 2885 KiB  
Article
Accuracy of Citrate Anticoagulant Amount, Volume, and Concentration in Evacuated Blood Collection Tubes Evaluated with UV Molecular Absorption Spectrometry on a Purified Water Model
by Nataša Gros, Tadej Klobučar and Klara Gaber
Molecules 2023, 28(2), 486; https://doi.org/10.3390/molecules28020486 - 4 Jan 2023
Cited by 3 | Viewed by 2754
Abstract
Citrate anticoagulant concentration affects the results of coagulation tests. Until now, the end user had no direct insight into the quality of evacuated blood collection tubes. By introducing an easy-to-perform UV spectrometric method for citrate determination on a purified water model, we enabled [...] Read more.
Citrate anticoagulant concentration affects the results of coagulation tests. Until now, the end user had no direct insight into the quality of evacuated blood collection tubes. By introducing an easy-to-perform UV spectrometric method for citrate determination on a purified water model, we enabled the evaluation of (1) the accuracy of the anticoagulant amount added into the tubes by a producer, (2) the accuracy of the volume of anticoagulant solution in the tube at the instant of examination, (3) the anticoagulant concentrations at a draw volume. We examined the Vacuette®, Greiner BIO-ONE, Vacutube, LT Burnik d.o.o., and BD Vacutainer® tubes. The anticoagulant amount added into the tubes during production had a relative bias between 3.2 and 23.0%. The anticoagulant volume deficiency at the instant of examination expressed as a relative bias ranged between −11.6 and −91.1%. The anticoagulant concentration relative bias after the addition of purified water in a volume that equalled a nominal draw volume extended from 9.3 to 25.7%. Draw-volume was mostly compliant during shelf life. Only Vacutube lost water over time. Contamination with potassium, magnesium, or both was observed in all the tubes but did not exceed a 0.21 mmol/L level. This study enables medical laboratories to gain insight into the characteristics of the citrate blood collection tubes as one of the preanalytical variables. In situations that require anticoagulant adjustment for accurate results, this can help make the right decisions. The methodology gives producers additional means of controlling the quality of their production process. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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13 pages, 3231 KiB  
Article
Thermal and Structural Characterization of Two Crystalline Polymorphs of Tafamidis Free Acid
by Norberto Masciocchi, Vincenzo Mirco Abbinante, Marco Zambra, Giuseppe Barreca and Massimo Zampieri
Molecules 2022, 27(21), 7411; https://doi.org/10.3390/molecules27217411 - 1 Nov 2022
Cited by 5 | Viewed by 2016
Abstract
Tafamidis, chemical formula C14H7Cl2NO3, is a drug used to delay disease progression in adults suffering from transthyretin amyloidosis, and is marketed worldwide under different tradenames as a free acid or in the form of its [...] Read more.
Tafamidis, chemical formula C14H7Cl2NO3, is a drug used to delay disease progression in adults suffering from transthyretin amyloidosis, and is marketed worldwide under different tradenames as a free acid or in the form of its meglumine salt. The free acid (CAS no. 594839-88-0) is reported to crystallize as distinct (polymorphic) crystal forms, the thermal stability and structural features of which remained thus far undisclosed. In this paper, we present—by selectively isolating highly pure batches of Tafamidis Form 1 and Tafamidis Form 4—the full characterization of these solids, in terms of crystal structures (determined using state-of-the-art structural powder diffraction methods) and spectroscopic and thermal properties. Beyond conventional thermogravimetric and calorimetric analyses, variable-temperature X-ray diffraction was employed to measure the highly anisotropic response of these (poly)crystalline materials to thermal stimuli and enabled the determination of the linear and volumetric thermal expansion coefficients and of the related indicatrix. Both crystal phases are monoclinic and contain substantially flat and π-π stacked Tafamidis molecules, arranged as centrosymmetric dimers by strong O-H···O bonds; weaker C-H···N contacts give rise, in both polymorphs, to infinite ribbons, which guarantee the substantial stiffness of the crystals in the direction of their elongation. Complete knowledge of the structural models will foster the usage of full-pattern quantitative phase analyses of Tafamidis in drug and polymorphic mixtures, an important aspect in both the forensic and the industrial sectors. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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18 pages, 1412 KiB  
Article
Development and Validation of a Sensitive and Specific LC-MS/MS Method for IWR-1-Endo, a Wnt Signaling Inhibitor: Application to a Cerebral Microdialysis Study
by Sreenath Nair, Abigail Davis, Olivia Campagne, John D. Schuetz and Clinton F. Stewart
Molecules 2022, 27(17), 5448; https://doi.org/10.3390/molecules27175448 - 25 Aug 2022
Cited by 1 | Viewed by 1703
Abstract
IWR-1-endo, a small molecule that potently inhibits the Wnt/β-catenin signaling pathway by stabilizing the AXIN2 destruction complex, can inhibit drug efflux at the blood–brain barrier. To conduct murine cerebral microdialysis research, validated, sensitive, and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods were used [...] Read more.
IWR-1-endo, a small molecule that potently inhibits the Wnt/β-catenin signaling pathway by stabilizing the AXIN2 destruction complex, can inhibit drug efflux at the blood–brain barrier. To conduct murine cerebral microdialysis research, validated, sensitive, and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods were used to determine IWR-1-endo concentration in the murine plasma and brain microdialysate. IWR-1-endo and the internal standard (ISTD) dabrafenib were extracted from murine plasma and microdialysate samples by a simple solid-phase extraction protocol performed on an Oasis HLB µElution plate. Chromatographic separation was executed on a Kinetex C18 (100A, 50 × 2.1 mm, 4 µm particle size) column with a binary gradient of water and acetonitrile, each having 0.1% formic acid, pumped at a flow rate of 0.6 mL/min. Detection by mass spectrometry was conducted in the positive selected reaction monitoring ion mode by monitoring mass transitions 410.40 > 344.10 (IWR-1-endo) and 520.40 > 307.20 (ISTD). The validated curve range of IWR-1-endo was 5–1000 ng/mL for the murine plasma method (r2 ≥ 0.99) and 0.5–500 ng/mL for the microdialysate method (r2 ≥ 0.99). The lower limit of quantification (LLOQ) was 5 ng/mL and 0.5 ng/mL for the murine plasma and microdialysate sample analysis method, respectively. Negligible matrix effects were observed in murine plasma and microdialysate samples. IWR-1-endo was extremely unstable in murine plasma. To improve the stability of IWR-1-endo, pH adjustments of 1.5 were introduced to murine plasma and microdialysate samples before sample storage and processing. With pH adjustment of 1.5 to the murine plasma and microdialysate samples, IWR-1-endo was stable across several tested conditions such as benchtop, autosampler, freeze–thaw, and long term at −80 °C. The LC-MS/MS methods were successfully applied to a murine pharmacokinetic and cerebral microdialysis study to characterize the unbound IWR-1-endo exposure in brain extracellular fluid and plasma. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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15 pages, 1982 KiB  
Article
A High-Throughput Clinical Laboratory Methodology for the Therapeutic Monitoring of Ibrutinib and Dihydrodiol Ibrutinib
by Gellért Balázs Karvaly, István Vincze, Alexandra Balogh, Zoltán Köllő, Csaba Bödör and Barna Vásárhelyi
Molecules 2022, 27(15), 4766; https://doi.org/10.3390/molecules27154766 - 25 Jul 2022
Viewed by 1708
Abstract
Ibrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical [...] Read more.
Ibrutinib (IBR) is an oral anticancer medication that inhibits Bruton tyrosine kinase irreversibly. Due to the high risk of adverse effects and its pharmacokinetic variability, the safe and effective use of IBR is expected to be facilitated by precision dosing. Delivering suitable clinical laboratory information on IBR is a prerequisite of constructing fit-for-purpose population and individual pharmacokinetic models. The validation of a dedicated high-throughput method using liquid chromatography–mass spectrometry is presented for the simultaneous analysis of IBR and its pharmacologically active metabolite dihydrodiol ibrutinib (DIB) in human plasma. The 6 h benchtop stability of IBR, DIB, and the active moiety (IBR + DIB) was assessed in whole blood and in plasma to identify any risk of degradation before samples reach the laboratory. In addition, four regression algorithms were tested to determine the optimal assay error equations of IBR, DIB, and the active moiety, which are essential for the correct estimation of the error of their future nonparametric pharmacokinetic models. The noncompartmental pharmacokinetic properties of IBR and the active moiety were evaluated in three patients diagnosed with chronic lymphocytic leukemia to provide a proof of concept. The presented methodology allows clinical laboratories to efficiently support pharmacokinetics-based precision pharmacotherapy with IBR. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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21 pages, 8986 KiB  
Article
Analytical Method Development for 19 Alkyl Halides as Potential Genotoxic Impurities by Analytical Quality by Design
by Kyoungmin Lee, Wokchul Yoo and Jin Hyun Jeong
Molecules 2022, 27(14), 4437; https://doi.org/10.3390/molecules27144437 - 11 Jul 2022
Cited by 9 | Viewed by 2548
Abstract
Major issues in the pharmaceutical industry involve efficient risk management and control strategies of potential genotoxic impurities (PGIs). As a result, the development of an appropriate method to control these impurities is required. An optimally sensitive and simultaneous analytical method using gas chromatography [...] Read more.
Major issues in the pharmaceutical industry involve efficient risk management and control strategies of potential genotoxic impurities (PGIs). As a result, the development of an appropriate method to control these impurities is required. An optimally sensitive and simultaneous analytical method using gas chromatography with a mass spectrometry detector (GC–MS) was developed for 19 alkyl halides determined to be PGIs. These 19 alkyl halides were selected from 144 alkyl halides through an in silico study utilizing quantitative structure–activity relationship (Q-SAR) approaches via expert knowledge rule-based software and statistical-based software. The analytical quality by design (QbD) approach was adopted for the development of a sensitive and robust analytical method for PGIs. A limited number of literature studies have reviewed the analytical QbD approach in the PGI method development using GC–MS as the analytical instrument. A GC equipped with a single quadrupole mass spectrometry detector (MSD) and VF-624 ms capillary column was used. The developed method was validated in terms of specificity, the limit of detection, quantitation, linearity, accuracy, and precision, according to the ICH Q2 guideline. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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10 pages, 1308 KiB  
Article
Wooden-Tip Electrospray Mass Spectrometry Characterization of Human Hemoglobin in Whole Blood Sample for Thalassemia Screening: A Pilot Study
by Tingting Huang, Ting Huang, Yongyi Zou, Kang Xie, Yinqin Shen, Wen Zhang, Shuhui Huang, Yanqiu Liu and Bicheng Yang
Molecules 2022, 27(12), 3952; https://doi.org/10.3390/molecules27123952 - 20 Jun 2022
Cited by 1 | Viewed by 1578
Abstract
Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS [...] Read more.
Traditional analytical methods for thalassemia screening are needed to process complicated and time-consuming sample pretreatment. In recent decades, ambient mass spectrometry (MS) approaches have been proven to be an effective analytical strategy for direct sample analysis. In this work, we applied ambient MS with wooden-tip electrospray ionization (WT-ESI) for the direct analysis of raw human blood samples that were pre-identified by gene detection. A total of 319 whole blood samples were investigated in this work, including 100 α-thalassemia carriers, 67 β-thalassemia carriers, and 152 control healthy samples. Only one microliter of raw blood sample was directly loaded onto the surface of the wooden tip, and then five microliters of organic solvent and a high voltage of +3.0 kV were applied onto the wooden tip to generate spray ionization. Multiply charged ions of human hemoglobin (Hb) were directly observed by WT-ESI-MS from raw blood samples. The signal ratios of Hb chains were used to characterize two main types of thalassemia (α and β types) and healthy control blood samples. Our results suggested that the ratios of charged ions to Hb chains being at +13 would be an indicator for β-thalassemia screening. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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11 pages, 452 KiB  
Article
Simultaneous Analysis of 19 Marker Components for Quality Control of Oncheong-Eum Using HPLC–DAD
by Chang-Seob Seo and Hyeun-Kyoo Shin
Molecules 2022, 27(9), 2992; https://doi.org/10.3390/molecules27092992 - 6 May 2022
Cited by 6 | Viewed by 1740
Abstract
Oncheong-eum (OCE) is a traditional herbal prescription made by combining Samul-tang and Hwangryunhaedok-tang. It is primarily used to treat gynecological disorders such as metrorrhagia and metrostaxis. In the present study, we focused on developing and validating a simultaneous assay for the quality control [...] Read more.
Oncheong-eum (OCE) is a traditional herbal prescription made by combining Samul-tang and Hwangryunhaedok-tang. It is primarily used to treat gynecological disorders such as metrorrhagia and metrostaxis. In the present study, we focused on developing and validating a simultaneous assay for the quality control of OCE using 19 marker components (gallic acid, 5-(hydroxymethyl)furfural, chlorogenic acid, geniposide, coptisine chloride, jatrorrhizine chloride, paeoniflorin, berberine chloride, palmatine chloride, ferulic acid, nodakenin, benzoic acid, baicalin, benzoylpaeoniflorin, wogonoside, baicalein, wogonin, decursin, and decursinol angelate). This analysis was performed using high-performance liquid chromatography coupled with a diode array detector, and chromatographic separation of the 19 markers was carried out using a SunFireTM C18 reversed-phase column and gradient elution conditions with two mobile phases (0.1% aqueous formic acid–0.1% formic acid in acetonitrile). The developed analytical method was validated through linearity, limits of detection and quantification, recovery, and precision. Under this assay, 19 markers in OCE samples were detected at not detected–9.62 mg/g. The analytical methods developed and validated in our research will have value as basic data for the quality control of related traditional herbal prescriptions as well as OCE. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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11 pages, 7576 KiB  
Article
Efficient Heparin Recovery from Porcine Intestinal Mucosa Using Zeolite Imidazolate Framework-8
by Mahmood Karimi Abdolmaleki, Deepak Ganta, Ali Shafiee, Carlo Alberto Velazquez and Devang P. Khambhati
Molecules 2022, 27(5), 1670; https://doi.org/10.3390/molecules27051670 - 3 Mar 2022
Cited by 6 | Viewed by 2229
Abstract
Heparin is one of the most valuable active pharmaceutical ingredients, and it is generally isolated from porcine intestinal mucosa. Traditionally, different types of commercial resins are employed as an adsorbent for heparin uptake; however, using new, less expensive adsorbents has attracted more interest [...] Read more.
Heparin is one of the most valuable active pharmaceutical ingredients, and it is generally isolated from porcine intestinal mucosa. Traditionally, different types of commercial resins are employed as an adsorbent for heparin uptake; however, using new, less expensive adsorbents has attracted more interest in the past few years to enhance the heparin recovery. Zeolite imidazolate framework-8 (ZIF-8), as a metal–organic framework (MOF) with a high surface area, porosity, and good stability at high temperatures, was selected to examine the heparin recovery. In this research, we demonstrate that ZIF-8 can recover up to ~70% (37 mg g−1) of heparin from porcine intestinal mucosa. A mechanistic study through kinetic and thermodynamic models on the adsorption revealed appropriate surface conditions for the adsorption of heparin molecules. The effect of different variables such as pH and temperature on heparin adsorption was also studied to optimize the recovery. This study is the first to investigate the usage of MOFs for heparin uptake. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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19 pages, 5044 KiB  
Article
Replicates Number for Drug Stability Testing during Bioanalytical Method Validation—An Experimental and Retrospective Approach
by Elżbieta Gniazdowska, Wojciech Goch, Joanna Giebułtowicz and Piotr J. Rudzki
Molecules 2022, 27(2), 457; https://doi.org/10.3390/molecules27020457 - 11 Jan 2022
Cited by 2 | Viewed by 1928
Abstract
Background: The stability of a drug or metabolites in biological matrices is an essential part of bioanalytical method validation, but the justification of its sample size (replicates number) is insufficient. The international guidelines differ in recommended sample size to study stability from no [...] Read more.
Background: The stability of a drug or metabolites in biological matrices is an essential part of bioanalytical method validation, but the justification of its sample size (replicates number) is insufficient. The international guidelines differ in recommended sample size to study stability from no recommendation to at least three quality control samples. Testing of three samples may lead to results biased by a single outlier. We aimed to evaluate the optimal sample size for stability testing based on 90% confidence intervals. Methods: We conducted the experimental, retrospective (264 confidence intervals for the stability of nine drugs during regulatory bioanalytical method validation), and theoretical (mathematical) studies. We generated experimental stability data (40 confidence intervals) for two analytes—tramadol and its major metabolite (O-desmethyl-tramadol)—in two concentrations, two storage conditions, and in five sample sizes (n = 3, 4, 5, 6, or 8). Results: The 90% confidence intervals were wider for low than for high concentrations in 18 out of 20 cases. For n = 5 each stability test passed, and the width of the confidence intervals was below 20%. The results of the retrospective study and the theoretical analysis supported the experimental observations that five or six repetitions ensure that confidence intervals fall within 85–115% acceptance criteria. Conclusions: Five repetitions are optimal for the assessment of analyte stability. We hope to initiate discussion and stimulate further research on the sample size for stability testing. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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15 pages, 1995 KiB  
Article
Development of Ecofriendly Derivative Spectrophotometric Methods for the Simultaneous Quantitative Analysis of Remogliflozin and Vildagliptin from Formulation
by Mahesh Attimarad, Katharigatta N. Venugopala, Bandar E. Al-Dhubiab, Rafea Elamin Elgack Elgorashe and Sheeba Shafi
Molecules 2021, 26(20), 6160; https://doi.org/10.3390/molecules26206160 - 12 Oct 2021
Cited by 14 | Viewed by 2659
Abstract
Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first [...] Read more.
Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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28 pages, 4468 KiB  
Article
Analysis of IV Drugs in the Hospital Workflow by Raman Spectroscopy: The Case of Piperacillin and Tazobactam
by Ioanna Chrisikou, Malvina Orkoula and Christos Kontoyannis
Molecules 2021, 26(19), 5879; https://doi.org/10.3390/molecules26195879 - 28 Sep 2021
Cited by 3 | Viewed by 2311
Abstract
Medical errors associated with IV preparation and administration procedures in a hospital workflow can even cost human lives due to the direct effect they have on patients. A large number of such incidents, which have been reported in bibliography up to date, indicate [...] Read more.
Medical errors associated with IV preparation and administration procedures in a hospital workflow can even cost human lives due to the direct effect they have on patients. A large number of such incidents, which have been reported in bibliography up to date, indicate the urgent need for their prevention. This study aims at proposing an analytical methodology for identifying and quantifying IV drugs before their administration, which has the potential to be fully harmonized with clinical practices. More specifically, it reports on the analysis of a piperacillin (PIP) and tazobactam (TAZ) IV formulation, using Raman spectroscopy. The simultaneous analysis of the two APIs in the same formulation was performed in three stages: before reconstitution in the form of powder without removing the substance out of the commercial glass bottle (non-invasively), directly after reconstitution in the same way, and just before administration, either the liquid drug is placed in the infusion set (on-line analysis) or a minimal amount of it is transferred from the IV bag to a Raman optic cell (at-line analysis). Except for the successful identification of the APIs in all cases, their quantification was also achieved through calibration curves with correlation coefficients ranging from 0.953 to 0.999 for PIP and from 0.965 to 0.997 for TAZ. In any case, the whole procedure does not need more than 10 min to be completed. The current methodology, based on Raman spectroscopy, outweighs other spectroscopic (UV/Vis, FT-IR/ATR) or chromatographic (HPLC, UHPLC) protocols, already applied, which are invasive, costly, time-consuming, not environmentally friendly, and require specialized staff and more complex sample preparation procedures, thus exposing the staff to hazardous materials, especially in cases of cytotoxic drugs. Such an approach has the potential to bridge the gap between experimental setup and clinical implementation through exploitation of already developed handheld devices, along with the presence of digital spectral libraries. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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12 pages, 1120 KiB  
Article
Photometric Determination of Iron in Pharmaceutical Formulations Using Double-Beam Direct Injection Flow Detector
by Stanislawa Koronkiewicz
Molecules 2021, 26(15), 4498; https://doi.org/10.3390/molecules26154498 - 26 Jul 2021
Cited by 3 | Viewed by 2679
Abstract
In this work, an innovative, flow-through, double-beam, photometric detector with direct injection of the reagents (double-DID) was used for the first time for the determination of iron in pharmaceuticals. For stable measurement of the absorbance, double paired emission-detection LED diodes and a log [...] Read more.
In this work, an innovative, flow-through, double-beam, photometric detector with direct injection of the reagents (double-DID) was used for the first time for the determination of iron in pharmaceuticals. For stable measurement of the absorbance, double paired emission-detection LED diodes and a log ratio precision amplifier have been applied. The detector was integrated with the system of solenoid micro-pumps. The micro-pumps helped to reduce the number of reagents used and are responsible for precise solution dispensing and propelling. The flow system is characterized by a high level of automation. The total iron was determined as a Fe(II) with photometric detection using 1,10-phenanthroline as a complexing agent. The optimum conditions of the propose analytical procedure were established and the method was validated. The calibration graph was linear in the range of 1 to 30 mg L−1. The limit of detection (LOD) was 0.5 mg L−1. The throughput of the method was 90 samples/hour. The repeatability of the method expressed as the relative standard deviation (R.S.D.) was 2% (n = 10). The method was characterized by very low consumption of reagents and samples (20 μL each) and a small amount of waste produced (about 540 µL per analysis). The proposed flow method was successfully applied for determination of iron in pharmaceutical products. The results were in good agreement with those obtained using the manual UV-Vis spectrophotometry and with values claimed by the manufacturers. The flow system worked very stably and was insensitive to bubbles appearing in the system. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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14 pages, 831 KiB  
Article
Development, Validation, and Application of the LC-MS/MS Method for Determination of 4-Acetamidobenzoic Acid in Pharmacokinetic Pilot Studies in Pigs
by Paulina Markowska, Zbigniew Procajło, Joanna Wolska, Jerzy Jan Jaroszewski and Hubert Ziółkowski
Molecules 2021, 26(15), 4437; https://doi.org/10.3390/molecules26154437 - 23 Jul 2021
Cited by 1 | Viewed by 2515
Abstract
Each drug has pharmacokinetics that must be defined for the substance to be used in humans and animals. Currently, one of the basic analytical tools for pharmacokinetics studies is high-performance liquid chromatography coupled with mass spectrometry. For this analytical method to be fully [...] Read more.
Each drug has pharmacokinetics that must be defined for the substance to be used in humans and animals. Currently, one of the basic analytical tools for pharmacokinetics studies is high-performance liquid chromatography coupled with mass spectrometry. For this analytical method to be fully reliable, it must be properly validated. Therefore, the aims of this study were to develop and validate a novel analytical method for 4-acetamidobenzoic acid, a component of the antiviral and immunostimulatory drug Inosine Pranobex, and to apply the method in the first pharmacokinetics study of 4-acetamidobenzoic acid in pigs after oral administration. Inosine Pranobex was administered under farm conditions to pigs via drinking water 2 h after morning feeding at doses of 20, 40, and 80 mg/kg. For sample preparation, we used liquid–liquid extraction with only one step—protein precipitation with 1 mL of acetonitrile. As an internal standard, we used deuterium labeled 4-acetamidobenzoic acid. The results indicate that the described method is replicable, linear (r2 ≥ 0.99), precise (2.11% to 13.81%), accurate (89% to 98.57%), selective, and sensitive (limit of quantitation = 10 ng/mL). As sample preparation requires only one step, the method is simple, effective, cheap, and rapid. The results of the pilot pharmacokinetics study indicate that the compound is quickly eliminated (elimination half-life from 0.85 to 1.42 h) and rapidly absorbed (absorption half-life from 0.36 to 2.57 h), and that its absorption increases exponentially as the dose is increased. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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17 pages, 935 KiB  
Article
HPLC-UV and GC-MS Methods for Determination of Chlorambucil and Valproic Acid in Plasma for Further Exploring a New Combined Therapy of Chronic Lymphocytic Leukemia
by Katarzyna Lipska, Anna Gumieniczek, Rafał Pietraś and Agata A. Filip
Molecules 2021, 26(10), 2903; https://doi.org/10.3390/molecules26102903 - 13 May 2021
Cited by 11 | Viewed by 2815
Abstract
High performance liquid chromatography with ultra-violet detection (HPLC-UV) and gas chromatography–mass spectrometry (GC-MS) methods were developed and validated for the determination of chlorambucil (CLB) and valproic acid (VPA) in plasma, as a part of experiments on their anticancer activity in chronic lymphocytic leukemia [...] Read more.
High performance liquid chromatography with ultra-violet detection (HPLC-UV) and gas chromatography–mass spectrometry (GC-MS) methods were developed and validated for the determination of chlorambucil (CLB) and valproic acid (VPA) in plasma, as a part of experiments on their anticancer activity in chronic lymphocytic leukemia (CLL). CLB was extracted from 250 µL of plasma with methanol, using simple protein precipitation and filtration. Chromatography was carried out on a LiChrospher 100 RP-18 end-capped column using a mobile phase consisting of acetonitrile, water and formic acid, and detection at 258 nm. The lowest limit of detection LLOQ was found to be 0.075 μg/mL, showing sufficient sensitivity in relation to therapeutic concentrations of CLB in plasma. The accuracy was from 94.13% to 101.12%, while the intra- and inter-batch precision was ≤9.46%. For quantitation of VPA, a sensitive GC-MS method was developed involving simple pre-column esterification with methanol and extraction with hexane. Chromatography was achieved on an HP-5MSUI column and monitored by MS with an electron impact ionization and selective ion monitoring mode. Using 250 µL of plasma, the LLOQ was found to be 0.075 μg/mL. The accuracy was from 94.96% to 109.12%, while the intra- and inter-batch precision was ≤6.69%. Thus, both methods fulfilled the requirements of FDA guidelines for the determination of drugs in biological materials. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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11 pages, 10635 KiB  
Article
Fast Screening of Biomembrane-Permeable Compounds in Herbal Medicines Using Bubble-Generating Magnetic Liposomes Coupled with LC–MS
by Xiaoting Gu, Dongwu Wang, Xin Wang, Youping Liu and Xin Di
Molecules 2021, 26(6), 1742; https://doi.org/10.3390/molecules26061742 - 20 Mar 2021
Cited by 2 | Viewed by 1918
Abstract
A novel strategy based on the use of bionic membrane camouflaged magnetic particles and LC–MS was developed to quickly screen the biomembrane-permeable compounds in herbal medicines. The bionic membrane was constructed by bubble-generating magnetic liposomes loaded with NH4HCO3 (BMLs). The [...] Read more.
A novel strategy based on the use of bionic membrane camouflaged magnetic particles and LC–MS was developed to quickly screen the biomembrane-permeable compounds in herbal medicines. The bionic membrane was constructed by bubble-generating magnetic liposomes loaded with NH4HCO3 (BMLs). The lipid bilayer structure of the liposomes enabled BMLs to capture biomembrane-permeable compounds from a herbal extract. The BMLs carrying the compounds were then separated from the extract by a magnetic field. Upon heat treatment, NH4HCO3 rapidly decomposed to form CO2 bubbles within the liposomal bilayer, and the captured compounds were released from BMLs and analyzed by LC–MS. Jinlingzi San (JLZS), which contains various natural ingredients, was chosen to assess the feasibility of the proposed method. As a result, nine potential permeable compounds captured by BMLs were identified for the first time. Moreover, an in vivo animal study found that most of the compounds screened out by the proposed method were absorbed into the blood. The study provides a powerful tool for rapid and simultaneous prediction of multiple biomembrane-permeable components. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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17 pages, 2695 KiB  
Article
Development, Validation, and Comparison of Two Mass Spectrometry Methods (LC-MS/HRMS and LC-MS/MS) for the Quantification of Rituximab in Human Plasma
by Aurélien Millet, Nihel Khoudour, Dorothée Lebert, Christelle Machon, Benjamin Terrier, Benoit Blanchet and Jérôme Guitton
Molecules 2021, 26(5), 1383; https://doi.org/10.3390/molecules26051383 - 4 Mar 2021
Cited by 13 | Viewed by 3410
Abstract
Rituximab is a chimeric immunoglobulin G1-kappa (IgG1κ) antibody targeting the CD20 antigen on B-lymphocytes. Its applications are various, such as for the treatment of chronic lymphoid leukemia or non-Hodgkin’s lymphoma in oncology, and it can also be used in the treatment of certain [...] Read more.
Rituximab is a chimeric immunoglobulin G1-kappa (IgG1κ) antibody targeting the CD20 antigen on B-lymphocytes. Its applications are various, such as for the treatment of chronic lymphoid leukemia or non-Hodgkin’s lymphoma in oncology, and it can also be used in the treatment of certain autoimmune diseases. Several studies support the interest in therapeutic drug monitoring to optimize dosing regimens of rituximab. Thus, two different laboratories have developed accurate and reproductive methods to quantify rituximab in human plasma: one using liquid chromatography quadripolar tandem mass spectrometer (LC-MS/MS) and the other, liquid chromatography orbitrap tandem mass spectrometer (LC-MS/HRMS). For both assays, quantification was based on albumin depletion or IgG-immunocapture, surrogate peptide analysis, and full-length stable isotope-labeled rituximab. With LC-MS/MS, the concentration range was from 5 to 500 µg/mL, the within- and between-run precisions were <8.5%, and the limit of quantitation was 5 µg/mL. With LC-MS/HRMS, the concentration range was from 10 to 200 µg/mL, the within- and between-run accuracy were <11.5%, and the limit of quantitation was 2 µg/mL. Rituximab plasma concentrations from 63 patients treated for vasculitis were compared. Bland–Altman analysis and Passing–Bablok regression showed the interchangeability between these two methods. Overall, these methods were robust and reliable and could be applied to routine clinical samples. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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13 pages, 2630 KiB  
Article
Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry
by Jangmi Choi, Min-Ho Park, Seok-Ho Shin, Jin-Ju Byeon, Byeong ill Lee, Yuri Park and Young G. Shin
Molecules 2021, 26(4), 1179; https://doi.org/10.3390/molecules26041179 - 22 Feb 2021
Cited by 2 | Viewed by 3210
Abstract
Sulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc-(SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identification studies in the brain for SAS [...] Read more.
Sulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc-(SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identification studies in the brain for SAS were quite limited. The aim of this study was to investigate the pharmacokinetics and metabolite identification of SAS and their distributions in mouse brain. Using in vivo brain exposure studies (neuro PK), the PK parameters of SAS was calculated for plasma as well as brain following intravenous and oral administration at 10 mg/kg and 50 mg/kg in mouse, respectively. In addition, in vivo metabolite identification (MetID) studies of SAS in plasma and brain were also conducted. The concentration of SAS in brain was much lower than that in plasma and only 1.26% of SAS was detected in mouse brain when compared to the SAS concentration in plasma (brain to plasma ratio (%): 1.26). In the MetID study, sulfapyridine (SP), hydroxy-sulfapyridine (SP-OH), and N-acetyl sulfapyridine (Ac-SP) were identified in plasma, whereas only SP and Ac-SP were identified as significant metabolites in brain. As a conclusion, our results suggest that the metabolites of SAS such as SP and Ac-SP might be responsible for the pharmacological effect in brain, not the SAS itself. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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Review

Jump to: Research

33 pages, 613 KiB  
Review
Recent Applications of Capillary Electrophoresis in the Determination of Active Compounds in Medicinal Plants and Pharmaceutical Formulations
by Marcin Gackowski, Anna Przybylska, Stefan Kruszewski, Marcin Koba, Katarzyna Mądra-Gackowska and Artur Bogacz
Molecules 2021, 26(14), 4141; https://doi.org/10.3390/molecules26144141 - 7 Jul 2021
Cited by 11 | Viewed by 4321
Abstract
The present review summarizes scientific reports from between 2010 and 2019 on the use of capillary electrophoresis to quantify active constituents (i.e., phenolic compounds, coumarins, protoberberines, curcuminoids, iridoid glycosides, alkaloids, triterpene acids) in medicinal plants and herbal formulations. The present literature review is [...] Read more.
The present review summarizes scientific reports from between 2010 and 2019 on the use of capillary electrophoresis to quantify active constituents (i.e., phenolic compounds, coumarins, protoberberines, curcuminoids, iridoid glycosides, alkaloids, triterpene acids) in medicinal plants and herbal formulations. The present literature review is founded on PRISMA guidelines and selection criteria were formulated on the basis of PICOS (Population, Intervention, Comparison, Outcome, Study type). The scrutiny reveals capillary electrophoresis with ultraviolet detection as the most frequently used capillary electromigration technique for the selective separation and quantification of bioactive compounds. For the purpose of improvement of resolution and sensitivity, other detection methods are used (including mass spectrometry), modifiers to the background electrolyte are introduced and different extraction as well as pre-concentration techniques are employed. In conclusion, capillary electrophoresis is a powerful tool and for given applications it is comparable to high performance liquid chromatography. Short time of execution, high efficiency, versatility in separation modes and low consumption of solvents and sample make capillary electrophoresis an attractive and eco-friendly alternative to more expensive methods for the quality control of drugs or raw plant material without any relevant decrease in sensitivity. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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24 pages, 623 KiB  
Review
Application of Capillary Electrophoresis to the Analysis of Bioactive Compounds in Herbal Raw Materials
by Anna Przybylska, Marcin Gackowski and Marcin Koba
Molecules 2021, 26(8), 2135; https://doi.org/10.3390/molecules26082135 - 8 Apr 2021
Cited by 20 | Viewed by 6730
Abstract
The article is a summary of scientific reports from the last 16 years (2005–2021) on the use of capillary electrophoresis to analyze polyphenolic compounds, coumarins, amino acids, and alkaloids in teas or different parts of plants used to prepare aqueous infusions, commonly known [...] Read more.
The article is a summary of scientific reports from the last 16 years (2005–2021) on the use of capillary electrophoresis to analyze polyphenolic compounds, coumarins, amino acids, and alkaloids in teas or different parts of plants used to prepare aqueous infusions, commonly known as “tea” or decoctions. This literature review is based on PRISMA guidelines and articles selected in base of criteria carried out using PICOS (Population, Intervention, Comparison, Outcome, Study type). The analysis showed that over 60% of articles included in this manuscript comes from China. The literature review shows that for the selective electrophoretic separation of polyphenolic and flavonoid compounds, the most frequently used capillary electromigration technique is capillary electrophoresis with ultraviolet detection. Nevertheless, the use of capillary electrophoresis-mass spectrometry allows for the sensitive determination of analytes with a lower limit of detection and gives hope for routine use in the analysis of functional foods. Moreover, using the modifications in electrochemical techniques allows methods sensitivity reduction along with the reduction of analysis time. Full article
(This article belongs to the Special Issue Analytical Techniques in Pharmaceutical and Biomedical Analysis)
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