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Advances in Pharmaceutical Analytical Technologies

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

Deadline for manuscript submissions: 30 November 2024 | Viewed by 13132

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Dr. Alexis Oliva

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Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38001 Tenerife, Spain
Interests: pharmaceutical; HPLC; analytical method; quality by design; design of experiments; validation; development and optimization; quality-control samples
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Special Issue Information

Dear Colleagues,

The use of analytical tools to determine pharmaceutical drugs for the rapid diagnosis of diseases is mandatory for every laboratory working in the field of bioanalysis. In the last few years, the development of new analytical technologies has widened the scope of application of such techniques to several areas, for instance, the development of new therapeutic agents and broader industries, alongside others.

Once the analytic method is selected, the next step consists of its development and optimization before validation. At present, the idea and principles of quality by design (QbD) are applied to the development of analytic methods. This type of study involves using the design of experiments (DoE) and multiple linear regressions (MLR) strategies. After the satisfactory development and optimization of an analytic method, it must be validated to demonstrate suitability for an intended purpose. For this, it can be assessed with two methods and aims: (i) “pre-study” validation, to demonstrate that it is able to provide appropriate accuracy and precision; (ii) “in-study” validation to verify whether the method remains valid over time. This is conducted by inserting quality control samples and through the use of control charts.

Presenting a very broad scope, this Special Issue welcomes full papers, short communications, and review articles on, but not limited to, new developments in bioanalysis, sample preparation, and the development and quantification of pharmaceuticals in complex matrices or in biological samples with applications in different analytical fields.

Dr. Alexis Oliva
Guest Editor

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Keywords

pharmaceutical
quality by design
design of experiments
analytical method
validation
development and optimization
quality control samples

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Published Papers (10 papers)

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Research

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18 pages, 5118 KiB

Open AccessArticle

Thermooxidation of Four Sartans: Kinetic Analysis Based on Thermo-Gravimetric Data

by Adriana Ledeţi, Bianca Baul, Amalia Ridichie, Denisa Ivan, Titus Vlase, Carmen Tomoroga, Anca Dragomirescu, Gabriela Vlase, Răzvan Adrian Bertici, Dana Emilia Man and Ionuţ Ledeţi

Molecules 2024, 29(23), 5527; https://doi.org/10.3390/molecules29235527 - 22 Nov 2024

Viewed by 245

Abstract

Angiotensin II receptor antagonists are tetrazole derivatives used in the treatment of high blood pressure, and are also indicated for the treatment of heart failure (NYHA class II-IV). They are used alone or in combination with other classes of antihypertensives or diuretics for the effective management of high blood pressure. In this study, we aim to evaluate the thermal stability and degradation kinetics for the principal compounds used in therapy from this class, namely telmisartan, valsartan, olmesartan medoxomil, and losartan potassium. To obtain the thermoanalytical data for the kinetic investigations, the TG and DTG curves were registered at five different heating rates (β = 2, 4, 6, 8, and 10 °C min⁻¹). The kinetic methods used were a preliminary ASTM E698 method and two isoconversional methods: Flynn–Wall–Ozawa and Friedman. For each molecule, the results showed complex decomposition processes consisting of complex reaction sequences. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

12 pages, 1629 KiB

Open AccessArticle

Rapid Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Total and Free Testosterone in Human Serum and Its Application to Monitoring Biomarker Response of Elite Athletes

by Jianli Zhang, Hang Yu, Yulin Shen, Xingya Yang and Yan Wang

Molecules 2024, 29(21), 5007; https://doi.org/10.3390/molecules29215007 - 23 Oct 2024

Viewed by 604

Abstract

Total testosterone (TT) and free testosterone (FT) are important biochemical markers for anabolism of the human body, and can also serve as early screening indicators for overtraining syndrome (OTS). Presently, there is no fast and reliable serum TT and FT determination method in the field of sport science that can meet the requirements of sports research. Thus, a rapid and accurate determination method for serum TT and FT to fill the gap is needed urgently in sports training. Herein, a simple and reliable liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of TT and FT in serum was developed and fully validated, followed by the application of professional athletes in training monitoring. Efficient pretreatments based on only one-step liquid–liquid extraction (LLE) for TT and one-step LLE after a 20 min ultrafiltration for FT were adopted in this study, and the isotope internal standard of testosterone-13C3 was used to ensure the reliability of the whole procedure. A linear range of four orders of magnitude with 0.02–100 ng/mL can meet the concentration range requirement between a higher limit for male TT and a lower limit for female FT. The accuracy, precision, stability, and matrix effect were all within the limits of the guidelines. The serum TT and FT levels of 200 professional athletes (98 male athletes and 102 female athletes) were investigated by this method. Serum TT, FT, and FT/TT levels of professional athletes were significantly higher than the general population, and serum TT levels were significantly higher by LC-MS/MS than by a chemiluminescence immunoassay. In conclusion, the LC-MS/MS method for TT and FT measurement developed in this study is time-saving and easy to operate, which can be used as a reliable method for the determination of serum TT and FT in sports training, offering valuable information for monitoring anabolism of athletes and screening OTS in the early stage. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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15 pages, 3738 KiB

Open AccessArticle

Determination of Cotinine, 3′-Hydroxycotinine and Nicotine 1′-Oxide in Urine of Passive and Active Young Smokers by LC-Orbitrap-MS/MS Technique

by Magdalena Szumska, Paweł Mroczek, Krystyna Tyrpień-Golder, Beata Pastuszka and Beata Janoszka

Molecules 2024, 29(15), 3643; https://doi.org/10.3390/molecules29153643 - 1 Aug 2024

Viewed by 863

Abstract

Tobacco smoke is probably the most significant factor conducing to toxic xenobiotics exposure to humans. The aim of the study was to develop a rapid and sensitive method for the determination of selected nicotine metabolites in urine of tobacco smokers and passive smokers. The method for removing protein and extracting the metabolites involved the centrifugation of urine with acetonitrile. Cotinine, trans-3′-hydroxycotinine, and (2′S)-nicotine 1’-oxide in the supernatant were determined using the LC-Orbitrap-MS/MS technique, with the selected ion monitoring (SIM) and parallel reaction monitoring (PRM) modes used. The recovery of these analytes added to the urine samples ranged from 72% to 101%. Repeatability and reproducibility were less than 3.1% and 10.1%, respectively. The study was carried out among medical students. The group was selected as representatives of young people and who as future physicians should be more aware of the effects of nicotine use. Concentration levels of cotinine and trans-3′-hydroxycotinine determined in ng/mL in the urine of cigarette smokers were 70- and 58-fold higher, respectively, compared to passive smokers. Higher concentrations were recorded in the urine of those passively exposed to tobacco smoke than in non-smokers, confirming that passive exposure to tobacco smoke is not harmless to the human body. However, no significant differences were observed in the concentration of (1′S,2′S)-nicotine 1′-oxide in the samples of individuals from various groups. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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14 pages, 4493 KiB

Open AccessArticle

Protein Tyrosine Phosphatase 1B Inhibitors of Pueraria lobata Based on the Spectrum–Effect Relationship by Q-Marker Selection

by Yong Zhang, Haipeng Liu, Tianci Lv, Mengqian Xiao and Guihua Gao

Molecules 2024, 29(12), 2731; https://doi.org/10.3390/molecules29122731 - 8 Jun 2024

Viewed by 881

Abstract

Pueraria lobata (P. lobata), a traditional anti-diabetic medicine mainly composed of flavonoids and isoflavones, has a long history in diabetes treatment in China. However, the anti-diabetic active component is still unclear. Recently, protein tyrosine phosphatase 1B (PTP1B) has been a hot therapeutic target by negatively regulating insulin signaling pathways. In this study, the spectrum–effect relationship analysis method was first used to identify the active components of P. lobata that inhibit PTP1B. The fingerprints of 12 batches of samples were established using high-performance liquid chromatography (HPLC), and sixty common peaks were identified. Meanwhile, twelve components were identified by a comparison with the standards. The inhibition of PTP1B activity was studied in vitro by using the p-nitrophenol method, and the partial least squares discriminant analysis, grey relational analysis, bivariate correlation analysis, and cluster analysis were used to analyze the bioactive compounds in P. lobata. Peaks 6, 9 (glycitin), 11 (genistin), 12 (4′-methoxypuerarin), 25, 34, 35, 36, 53, and 59 were considered as potentially active substances that inhibit PTP1B. The in vitro PTP1B inhibitory activity was confirmed by glycitin, genistin, and 4′-methoxypuerarin. The IC₅₀s of the three compounds were 10.56 ± 0.42 μg/mL, 16.46 ± 0.29 μg/mL, and 9.336 ± 0.56 μg/mL, respectively, indicating the obvious PTP1B inhibitory activity. In brief, we established an effective method to identify PTP1B enzyme inhibitors in P. lobata, which is helpful in clarifying the material basis of P. lobata on diabetes. Additionally, it is evident that the spectrum–effect relationship method serves as an efficient approach for identifying active compounds, and this study can also serve as a reference for screening bioactive constituents in traditional Chinese medicine. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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11 pages, 1771 KiB

Open AccessArticle

Study of Bitespiramycin Distribution in Rats and Cerebrospinal Fluid of Patients by a Sensitive LC-MS/MS Method with Rapid Sample Preparation

by Yujie Zhang, Jingjie Cao, Jiahan Su, Tingting He, Qianru Wang, Feng Wei, Xin Guo, Qibing Mei and Jing Zeng

Molecules 2024, 29(5), 1037; https://doi.org/10.3390/molecules29051037 - 28 Feb 2024

Viewed by 973

Abstract

Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC–MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using n-butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC–MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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13 pages, 1031 KiB

Open AccessArticle

Ultrasound-Assisted Extraction, Followed by Gas Chromatography–Mass Spectrometry for the Simultaneous Quantification of Ethinyl Estradiol and Drospirenone in Contraceptive Formulations

by Javier Peña, Iria González-Mariño and José L. Pérez Pavón

Molecules 2023, 28(13), 4978; https://doi.org/10.3390/molecules28134978 - 25 Jun 2023

Cited by 2 | Viewed by 1331

Abstract

Contraceptive tablets typically contain a combination of two synthetic versions of an estrogen and a progestogen, which work together to inhibit the ovulation process. An accurate and precise quantification of these components is essential for contraceptive producers. In this study, we have developed the first gas chromatography–mass spectrometry (GC–MS) method for the simultaneous quantification of 17α-ethinyl estradiol (EE) and drospirenone (DP) in contraceptive formulations. Under the final working conditions, analytes were extracted from the solid by ultrasound-assisted extraction (15 min) in methanol. The resulting suspension was diluted in ethyl acetate, subjected to centrifugation and, finally, the supernatant was directly injected into the GC–MS system. No derivatization reagents were utilized. To correct for instrumental variations, calibration was performed using the internal standard method, with cholesterol as the internal standard. A good linearity was achieved throughout the calibration range for both EE (3–12 µg mL⁻¹) and DP (300–1200 µg mL⁻¹), with R² values exceeding 0.99. Trueness, assessed in terms of percentages of recovery, was also found to be satisfactory for both analytes, with recovery rates of 106 ± 8% for EE and 93 ± 9% for DP. Furthermore, intra-day and inter-day precision studies yielded relative standard deviation values below 6% for both analytes. In terms of sensitivity, the instrumental limits of detection were 0.25 µg mL⁻¹ for EE and 6.6 µg mL⁻¹ for DP, and the instrumental limits of quantification 0.82 µg mL⁻¹ for EE and 22 µg mL⁻¹ for DP. The method was successfully applied to the analysis of contraceptive tablets from three different pharmaceutical companies. No differences were observed between the measured and the declared amount of active principle per tablet, demonstrating the applicability of the procedure. In addition, a stability study conducted on both the standards and sample extracts demonstrated that they can be stored at room temperature for a minimum period of seven days. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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12 pages, 1977 KiB

Open AccessArticle

Multi-Detection Size Exclusion Chromatography as an Advanced Tool for Monitoring Enzyme–Antibody Conjugation Reaction and Quality Control of a Final Product

by Adela Štimac, Tihana Kurtović and Beata Halassy

Molecules 2023, 28(11), 4567; https://doi.org/10.3390/molecules28114567 - 5 Jun 2023

Viewed by 2243

Abstract

The multi-detection size exclusion chromatography (SEC) has been recognized as an advanced analytical technique for the characterization of macromolecules and process control, as well as the manufacturing and formulation of biotechnology products. It reveals reproducible molecular characterization data, such as molecular weight and its distribution, and the size, shape, and composition of the sample peaks. The aim of this work was to investigate the potential and suitability of the multi-detection SEC as a tool for surveillance over the molecular processes during the conjugation reaction between the antibody (IgG) and horseradish peroxidase (HRP), and demonstrate the plausibility of its application in the quality control of the final product, the IgG-HRP conjugate. Guinea pig anti-Vero IgG-HRP conjugate was prepared using a modified periodate oxidation method, based on periodate oxidation of the carbohydrate side chains of HRP, followed by the formation of Schiff bases between the activated HRP and amino groups of the IgG. The quantitative molecular characterization data of the starting samples, intermediates, and final product were obtained by multi-detection SEC. Titration of the prepared conjugate was performed by the ELISA and its optimal working dilution was determined. This methodology proved to be a promising and powerful technology for the IgG-HRP conjugate process control and development, as well as for the quality control of the final product, as verified by the analysis of several commercially available reagents. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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14 pages, 2286 KiB

Open AccessArticle

Development and Validation of Green and High-Throughput Microwell Spectrophotometric Assay for the Determination of Selective Serotonin Reuptake Inhibitors in Their Pharmaceutical Dosage Forms

by Ibrahim A. Darwish and Nourah Z. Alzoman

Molecules 2023, 28(10), 4221; https://doi.org/10.3390/molecules28104221 - 21 May 2023

Cited by 10 | Viewed by 1608

Abstract

This study describes the development and validation of a new green and high-throughput microwell spectrophotometric assay (MW-SPA) for the determination of three selective serotonin reuptake inhibitors (SSRIs) in their pharmaceutical dosage forms. These SSRIs are fluoxetine, fluvoxamine, and paroxetine, the most prescribed drugs for the treatment of depression. The proposed assay was based on the formation of orange-colored N-substituted naphthoquinone derivatives upon the reaction of SSRIs with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline media. The assay was conducted in 96-microwell assay plates, and the absorbances of the reaction products were measured by a microplate reader at their maximum absorbance wavelengths. The optimum conditions of the reaction were refined and established. Under these conditions, calibration curves were generated, and linear regression equations were computed. The linear relations between the absorbances and drug concentrations were linear with good correlation coefficients (0.9992–0.9997) in the range of 2–80 µg/mL. The assay limits of detection were in the range of 1.5–4.2 µg/mL. The precision was satisfactory as the values of relative standard deviation did not exceed 1.70%. The accuracy of the assay was ≥98.2%. The proposed MW-SPA was successfully applied to the analysis of the SSRIs in their pharmaceutical dosage forms with acceptable accuracy and precision; the label claims were 99.2–100.5% (±0.96–1.35%). The results of the proposed MW-SPA were compared with those of the official/pre-validated assays by statistical analysis with respect to the accuracy (by t-test) and precision (by F-test). No significant differences were found between the calculated and theoretical values of the t- and F-tests at the 95% confidence level, proving similar accuracy and precision in the determination of SSRIs by both assays. The greenness of the proposed assay was confirmed by two metric tools. In addition, the assay is characterized with a high-throughput property which enables the simultaneous analysis of many samples in a short time. Therefore, the assay is a valuable tool for rapid routine application in pharmaceutical quality control units for the determination of the investigated SSRIs. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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Review

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38 pages, 10318 KiB

Open AccessReview

Pyrrolizidine Alkaloids as Hazardous Toxins in Natural Products: Current Analytical Methods and Latest Legal Regulations

by Agnieszka Lis-Cieplak, Katarzyna Trześniowska, Krzysztof Stolarczyk and Elżbieta U. Stolarczyk

Molecules 2024, 29(14), 3269; https://doi.org/10.3390/molecules29143269 - 10 Jul 2024

Viewed by 1620

Abstract

Pyrrolizidine alkaloids (PAs) are toxic compounds that occur naturally in certain plants, however, there are many secondary pathways causing PA contamination of other plants, including medicinal herbs and plant-based food products, which pose a risk of human intoxication. It is proven that chronic exposure to PAs causes serious adverse health consequences resulting from their cytotoxicity and genotoxicity. This review briefly presents PA occurrence, structures, chemistry, and toxicity, as well as a set of analytical methods. Recently developed sensitive electrochemical and chromatographic methods for the determination of PAs in honey, teas, herbs, and spices were summarized. The main strategies for improving the analytical efficiency of PA determination are related to the use of mass spectrometric (MS) detection; therefore, this review focuses on advances in MS-based methods. Raising awareness of the potential health risks associated with the presence of PAs in food and herbal medicines requires ongoing research in this area, including the development of sensitive methods for PA determination and rigorous legal regulations of PA intake from herbal products. The maximum levels of PAs in certain products are regulated by the European Commission; however, the precise knowledge about which products contain trace but significant amounts of these alkaloids is still insufficient. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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13 pages, 1500 KiB

Open AccessReview

Research Progress of Ferula ferulaeoides: A Review

by Zhengqiong Chen, Gang Zhou and Shengjun Ma

Molecules 2023, 28(8), 3579; https://doi.org/10.3390/molecules28083579 - 19 Apr 2023

Cited by 5 | Viewed by 1896

Abstract

Ferula ferulaeoides (Steud.) Korov is one of the traditional ethnic medicines in Xinjiang Uygur and Kazakh of China, which mainly contains volatile oils, terpenoids, coumarins and other chemical components. Previous work has shown that F. ferulaeoides exhibited insecticide, antibacterial, antitumor properties, and so on. In this paper, the chemical composition, pharmacological activity, and quality control of F. ferulaeoides were reviewed, and the application of F. ferulaeoides in the food industry was explored, so as to provide some reference for the quality evaluation of F. ferulaeoides and its further development and utilization. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Analytical Technologies)

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