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14 pages, 992 KiB  
Article
Development and Validation of a Highly Sensitive LC–MS/MS Method for the Precise Quantification of Sitagliptin in Human Plasma and Its Application to Pharmacokinetic Study
by Yuna Song, Wang-Seob Shim, Eunseo Song, Yebeen Park, Bo-Hyung Kim, Sangmin Lee, Eun Kyoung Chung and Kyung-Tae Lee
Molecules 2025, 30(14), 2995; https://doi.org/10.3390/molecules30142995 - 16 Jul 2025
Viewed by 303
Abstract
Sitagliptin is an orally bioavailable selective DPP4 inhibitor that reduces blood glucose levels without significant increases in hypoglycemia. The aim of this study was to design and validate an innovative, rapid, and highly sensitive LC–MS/MS assay for the precise measurement of sitagliptin concentrations [...] Read more.
Sitagliptin is an orally bioavailable selective DPP4 inhibitor that reduces blood glucose levels without significant increases in hypoglycemia. The aim of this study was to design and validate an innovative, rapid, and highly sensitive LC–MS/MS assay for the precise measurement of sitagliptin concentrations in human plasma. This analytical method, utilizing sitagliptin-d4 as the internal standard, is performed using only 100 μL of plasma and a liquid–liquid extraction procedure based on methyl tert-butyl ether (MTBE). Chromatographic separation is expertly achieved with a Kinetex® C18 column under isocratic elution, employing a perfect 1:1 blend of 5 mM ammonium acetate (with 0.04% formic acid) and acetonitrile, and maintaining an efficient flow rate of 0.2 mL/min. Detection occurs in positive ionization mode through multiple reaction monitoring, precisely targeting transitions of m/z 408.2 → 193.0 for sitagliptin and 412.2 → 239.1 for the IS. The total runtime of this assay is under 2 min. Comprehensive validation in line with MFDS and FDA criteria demonstrates outstanding linearity (5–1000 ng/mL, r2 > 0.998), alongside impressive levels of accuracy, precision, recovery and sample stability. Due to its minimal sample requirement and high-throughput capability, the validated approach is highly appropriate for pharmacokinetic and bioequivalence assessments involving sitagliptin. Full article
(This article belongs to the Special Issue The Application of LC-MS in Pharmaceutical Analysis)
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16 pages, 689 KiB  
Article
Quantification of Total and Unbound Selinexor Concentrations in Human Plasma by a Fully Validated Liquid Chromatography-Tandem Mass Spectrometry Method
by Suhyun Lee, Seungwon Yang, Hyeonji Kim, Wang-Seob Shim, Eunseo Song, Seunghoon Han, Sung-Soo Park, Suein Choi, Sungpil Han, Sung Hwan Joo, Seok Jun Park, Beomjin Shin, Donghyun Kim, Hyeon Su Kim, Kyung-Tae Lee and Eun Kyoung Chung
Pharmaceutics 2025, 17(7), 919; https://doi.org/10.3390/pharmaceutics17070919 - 16 Jul 2025
Viewed by 320
Abstract
Background/Objectives: Selinexor is a selective nuclear-export inhibitor approved for hematologic malignancies, characterized by extensive plasma protein binding (>95%). However, a validated analytical method to accurately measure the clinically relevant unbound fraction of selinexor in human plasma has not yet been established. This study [...] Read more.
Background/Objectives: Selinexor is a selective nuclear-export inhibitor approved for hematologic malignancies, characterized by extensive plasma protein binding (>95%). However, a validated analytical method to accurately measure the clinically relevant unbound fraction of selinexor in human plasma has not yet been established. This study aimed to develop a fully validated bioanalytical assay for simultaneous quantification of total and unbound selinexor concentrations in human plasma. Methods: We established and fully validated an analytical method based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) capable of quantifying total and unbound selinexor concentrations in human plasma. Unbound selinexor was separated using ultrafiltration, and selinexor was efficiently extracted from 50 μL of plasma by liquid–liquid extraction. Chromatographic separation was achieved on a C18 column using an isocratic mobile phase (0.1% formic acid:methanol, 12:88 v/v) with a relatively short runtime of 2.5 min. Results: Calibration curves showed excellent linearity over a range of 5–2000 ng/mL for total selinexor (r2 ≥ 0.998) and 0.05–20 ng/mL for unbound selinexor (r2 ≥ 0.995). The precision (%CV ≤ 10.35%) and accuracy (92.5–104.3%) for both analytes met the regulatory criteria. This method successfully quantified selinexor in plasma samples from renally impaired patients with multiple myeloma, demonstrating potential inter-individual differences in unbound drug concentrations. Conclusions: This validated bioanalytical assay enables precise clinical pharmacokinetic assessments in a short runtime using a small plasma volume and, thus, assists in individualized dosing of selinexor, particularly for renally impaired patients with altered protein binding. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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19 pages, 1810 KiB  
Article
Analysis of Aspirin and Dipyridamole in a Modern Pharmaceutical Formulation-Drug Release Study and Permeability Assessment
by Georgios Kamaris, Nikoletta Pantoudi, Konstantina Chachlioutaki and Catherine K. Markopoulou
Appl. Sci. 2025, 15(11), 6048; https://doi.org/10.3390/app15116048 - 28 May 2025
Viewed by 611
Abstract
Oral administration of dipyridamole (DIP) with acetylsalicylic acid (ACA) is recommended in thromboembolic conditions or for the treatment of myocardial infarction and stroke. The present study presents an alternative dosage form of these two active ingredients, consisting of a honey core and a [...] Read more.
Oral administration of dipyridamole (DIP) with acetylsalicylic acid (ACA) is recommended in thromboembolic conditions or for the treatment of myocardial infarction and stroke. The present study presents an alternative dosage form of these two active ingredients, consisting of a honey core and a dark chocolate coating. The composition masks the bitter taste, is palatable and ensures compliance of a wide range of patients, mainly pediatric. For the simultaneous quantitative determination of the analytes, a Diode Array Detector/Fluorescence Detector (HPLC-DAD/FLD) method was used with a C18 column (250 mm × 4.6 mm, 5 μm) and an isocratic two-phase system (A: H2O 0.2% formic acid—B: Acetonitrile-H2O 90:10 v/v) 65:35 v/v. The method was validated according to ICH guidelines (r2 > 0.999, RSD < 2.3%, % Recovery > 95.4%), and a stability study of the two active ingredients as well as salicylic acid (SAL), which is a hydrolysis product of ACA, was followed. Finally, a digestion protocol (oral cavity–stomach–intestine) for edible materials was applied to determine the release rate of ACA, DIP and SAL in the gastrointestinal tract, while an in vitro permeability study (Papp) was subsequently performed in Franz cells. The results show satisfactory behavior of ACA and DIP and provide a trigger for further studies of the formulation. Full article
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35 pages, 4271 KiB  
Article
Optimized and Validated Stability-Indicating RP-HPLC Method for Comprehensive Profiling of Process-Related Impurities and Stress-Induced Degradation Products in Rivaroxaban (XARELTO)®
by Aktham H. Mestareehi
Int. J. Mol. Sci. 2025, 26(10), 4744; https://doi.org/10.3390/ijms26104744 - 15 May 2025
Cited by 1 | Viewed by 691
Abstract
An isocratic reverse-phase high-performance liquid chromatography (RP-HPLC) method, coupled with photodiode array detection (PDA), was developed for the identification and characterization of stress degradation products and an unknown process-related impurity of rivaroxaban in bulk drug form. Rivaroxaban, a selective and direct Factor Xa [...] Read more.
An isocratic reverse-phase high-performance liquid chromatography (RP-HPLC) method, coupled with photodiode array detection (PDA), was developed for the identification and characterization of stress degradation products and an unknown process-related impurity of rivaroxaban in bulk drug form. Rivaroxaban, a selective and direct Factor Xa inhibitor, underwent forced degradation under hydrolytic (acidic, alkaline, and neutral), photolytic, thermal, and oxidative stress conditions, following the ICH’s guidelines. The drug displayed significant susceptibility to acid, base, and oxidative environments leading to the formation of eleven degradation products. All degradation products, along with process impurities and Rivaroxaban, were effectively separated using a (4.6 × 250 mm, 5 µm) C18 Thermo ODS Hypersil column at ambient temperature. The mobile phase composed of acetonitrile and monobasic potassium phosphate (pH 2.9) in a 30:70 (v/v) ratio, with a flow rate of 1.0 mL/min, and detection was carried out at 249 nm. The LC-PDA method was validated in accordance with the ICH’s guidelines and USP38-NF33, demonstrating specificity, linearity, accuracy, precision, and robustness. Recovery studies showed results within the range of 98.6–103.4%, with a % RSD LT 2%. The limits of detection (LOD) and quantitation (LOQ) for rivaroxaban were determined to be 0.30 ppm and 1.0 ppm, respectively. Stress studies confirmed that the degradation products did not interfere with rivaroxaban detection, establishing the method as stability-indicating. Specific impurities were identified, including impurity G at 2.79 min, impurity D at 3.50 min, impurity H at 5.32 min, impurity C at 6.14 min, impurity E at 8.36 min, impurity A at 9.03 min, and impurity F at 9.49 min. Additionally, several unknown impurities were observed at 3.20, 4.00, 4.59, and 4.77 min. Statistical evaluation confirmed the method’s reliability, making it suitable for routine analysis, quality control of raw materials, formulations of varying strengths, dissolution studies, and bioequivalence assessments of rivaroxaban formulations. Full article
(This article belongs to the Section Biochemistry)
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11 pages, 1236 KiB  
Article
Determination of Dronedarone and Debutyldronedarone in Human Plasma by HPLC-UV
by Paweł K. Kunicki and Adam Stocki
Int. J. Mol. Sci. 2025, 26(9), 4304; https://doi.org/10.3390/ijms26094304 - 1 May 2025
Viewed by 367
Abstract
Dronedarone (DRO) is an antiarrhythmic drug that should be used under close supervision, and therapeutic drug monitoring (TDM) may be one of the tools supporting pharmacotherapy. The aim of our study was to develop an economical HPLC method for determining DRO and its [...] Read more.
Dronedarone (DRO) is an antiarrhythmic drug that should be used under close supervision, and therapeutic drug monitoring (TDM) may be one of the tools supporting pharmacotherapy. The aim of our study was to develop an economical HPLC method for determining DRO and its active metabolite debutyldronedarone (DBD) in human plasma. An HPLC isocratic system with a manual injector was applied. The separation was performed on a Supelcosil LC-CN column (150 × 4.6 mm, 5 µm) at an ambient temperature. The mobile phase was a mixture of CH3OH:CH3CN:H2O:0.5 M KH2PO4 (170:85:237.2:7.8 (v/v)) + 0.1 mL 85% H3PO4 pumped at a flow rate of 1.8 mL/min. The UV detection was set at λ = 290 nm. A methyl tert-butyl ether was used for the extraction from a 0.4 mL alkalized plasma sample. The analytes were eluted at retention times of 4.0 min, 5.2 min and 6.0 min for DBD, internal standard bepridil and DRO, respectively. The method was calibrated in the range of 10–1000 ng/mL for both DRO and DBD. The adequate specificity, accuracy and precision were demonstrated in accordance with EMA guidelines, i.e., ≤15% (≤20% for the LLOQ), which ensures the reliability of the measurements. This method can be recommended for laboratories with basic HPLC equipment for TDM, adherence assessments and even in PK studies during chronic DRO therapy. Full article
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15 pages, 1924 KiB  
Article
Determination of Fluconazole in Children in Small Blood Volumes Using Volumetric Absorptive Microsampling (VAMS) and Isocratic High-Performance Liquid Chromatography–Ultraviolet (HPLC–UV) Detection
by Franziska Zimbelmann, Andreas H. Groll and Georg Hempel
Pharmaceutics 2025, 17(5), 592; https://doi.org/10.3390/pharmaceutics17050592 - 1 May 2025
Viewed by 427
Abstract
Objectives: A simple method for quantifying fluconazole in small blood volumes has been developed using volumetric absorptive microsampling (VAMS®) technology and isocratic high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Methods: For sample collection, Mitra® devices are used [...] Read more.
Objectives: A simple method for quantifying fluconazole in small blood volumes has been developed using volumetric absorptive microsampling (VAMS®) technology and isocratic high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Methods: For sample collection, Mitra® devices are used to keep the sample volume at 10 µL. For the quantitative determination of fluconazole, the Mitra® samples are extracted using acetonitrile as the extraction agent, containing 2-(4-chlorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-ol as the internal standard. A Synergi 4 μm Polar-RP 80 Å (150 × 2 mm) column forms the stationary phase, and a mixture of acetonitrile and phosphate buffer is the mobile phase. The UV detection is set at a wavelength of 210 nm. The therapeutic concentration range of 5 to 160 mg/L is covered, and the linear equation with 1/x2 weighting is used to determine unknown samples. This method has been validated according to the current EMA and FDA guidelines for bioanalytical methods. Results: The validation data obtained after analysing whole blood samples (EDTA) showed within- and between-run accuracy between 94.4% and 115% and precision between 0.4% and 9.4%, respectively. A lower limit of quantification (LLOQ) of 5 mg/L was sufficient for therapeutic drug monitoring in paediatric patients receiving fluconazole as antifungal prophylaxis after haematopoietic cell transplantation. Conclusions: So far, 211 samples from 49 patients were successfully analysed, and concentrations between 5.84 mg/L and 107 mg/L were determined for whole blood Mitra® samples. To our knowledge, this is the first application of VAMS® technology using simple and cheap HPLC-UV quantification. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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12 pages, 1231 KiB  
Article
Enantio- and Chemo-Selective HPLC Analysis of Silodosin on an Amylose-Based Chiral Stationary Phase
by Daniele Sadutto, Francesca Romana Mammone, Giulia D’Ettorre, Leo Zanitti, Daniela De Orsi, Romina Alfonsi, Francesca Prestinaci and Roberto Cirilli
Molecules 2025, 30(9), 1966; https://doi.org/10.3390/molecules30091966 - 29 Apr 2025
Viewed by 435
Abstract
A direct enantio- and chemo-selective high-performance liquid chromatographic method was developed for determining the enantiomeric impurity of the chiral active pharmaceutical ingredient silodosin. The simultaneous separation of enantiomers of silodosin and its main organic related substances listed in the Japanese Pharmacopoeia (JP) monograph [...] Read more.
A direct enantio- and chemo-selective high-performance liquid chromatographic method was developed for determining the enantiomeric impurity of the chiral active pharmaceutical ingredient silodosin. The simultaneous separation of enantiomers of silodosin and its main organic related substances listed in the Japanese Pharmacopoeia (JP) monograph for drug substance was achieved on Chiralpak AD-3 (250 mm × 4.6 mm, 3 μm) column under normal-phase isocratic conditions. The optimized conditions employed the mixture n-heptane-ethanol-diethylamine (70:30:0.1) (v/v/v) as a mobile phase and a temperature of 35 °C. The complete separation of the enantiomers of silodosin and its main impurities was obtained within 12 min. The chromatographic method has been validated according to the International Conference on Harmonization (ICH) guidelines and compared with the method reported in the JP monograph. The standard curve for silodosin exhibited linearity (R2 > 0.999) within the concentration range of 1.13–2500 µg mL−1. The Chiralpak AD-3 has demonstrated a remarkable level of efficiency, enabling the attainment of limits of quantitation for silodosin of 1.13 µg mL−1 (equivalent to 0.057% of a sample solution of 2 mg mL−1) and ranging from 0.48 µg mL−1 to 1.94 µg mL−1 for other impurities. Full article
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14 pages, 1997 KiB  
Article
Development and Validation of an HPLC-MS/MS Method for the Simultaneous Quantification of Vitexin and Isovitexin in Rabbit Plasma: Pharmacokinetic Insights on a Microcapsule Formulation
by Duc Tuan Nguyen, Trung Nguyen Nguyen Le, Duc Kien Ngo, Hien Minh Khuu, Khang Thien Tran, Hoang Thanh Le, Hung Viet Tran, Truong-Thang Nguyen Phan, Vo Thi Kim Khuyen, Han Hoang Do, Nhu Huynh Mai and Quan Minh Le
Molecules 2025, 30(8), 1690; https://doi.org/10.3390/molecules30081690 - 10 Apr 2025
Cited by 2 | Viewed by 782
Abstract
Vitexin and isovitexin are natural flavone C-glucosides that have numerous benefits for human health. However, their low oral bioavailability and poor gastrointestinal absorption dramatically restrict their potential medicinal uses. To overcome this challenge, chitosan-coated alginate microcapsules were prepared for intragastrical administration to rabbits. [...] Read more.
Vitexin and isovitexin are natural flavone C-glucosides that have numerous benefits for human health. However, their low oral bioavailability and poor gastrointestinal absorption dramatically restrict their potential medicinal uses. To overcome this challenge, chitosan-coated alginate microcapsules were prepared for intragastrical administration to rabbits. An LC-MS/MS method was developed and validated for the simultaneous determination of vitexin and isovitexin in the plasma of treated rabbits, using salicylic acid as the internal standard. Raw rabbit plasma samples were deproteinized using acetonitrile as a precipitation agent. Chromatographic separation was performed on a reversed-phase C18 column (100 mm × 4.6 mm, 3.5 µm), with an isocratic mobile solvent system comprising methanol and 0.1% acetic acid (40:60) as the mobile phase. All the analytes and the internal standard were ionized on a triple quadrupole mass spectrometer and electrospray ionization, operating in negative mode and multiple reaction monitoring. The analytical approach developed underwent validation in terms of system suitability, specificity, selectivity, LLOQ of 2 ng/mL, linearity (2.0–200 ng/mL, R2 > 0.99), accuracy (the intra- and inter-day from 94 to 110% with the relative standard deviations no more than 8.7%, precision with the recoveries from 97% to 102%, matrix effect (90–100%), carry-over, dilution integrity (2 times), and stability at room and frozen temperature for up to 1 month, and all the parameters met FDA and EMA requirements for bioanalytical methods. The validated procedure was applied to measure the absorption of vitexin and isovitexin from encapsulated extracts in a pilot pharmacokinetic study on rabbit plasma. Compared to the raw traditional extracts, the microcapsules enhanced the bioavailability of vi-texin and isovitexin regarding Cmax and AUC values. Full article
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15 pages, 6078 KiB  
Article
Developing a Quantitative Profiling Method for Detecting Free Fatty Acids in Crude Lanolin Based on Analytical Quality by Design
by Sihan Liu, Shaohua Wu, Hao Zhang and Xingchu Gong
Chemosensors 2025, 13(4), 126; https://doi.org/10.3390/chemosensors13040126 - 3 Apr 2025
Viewed by 723
Abstract
In this study, a quantitative profiling method for detecting free fatty acids in crude lanolin based on the Quality by Design (QbD) concept was developed. High-performance liquid chromatography (HPLC) equipped with a charged aerosol detector (CAD) and a Proshell 120 EC C18 column [...] Read more.
In this study, a quantitative profiling method for detecting free fatty acids in crude lanolin based on the Quality by Design (QbD) concept was developed. High-performance liquid chromatography (HPLC) equipped with a charged aerosol detector (CAD) and a Proshell 120 EC C18 column was employed for the separation of crude lanolin components. Initially, the analytical target profile and critical method attributes were defined. Potential critical method parameters, including column temperature, flow rate, isocratic run time, gradient end organic phase ratio, and gradient time, were identified using fishbone diagrams and single-factor experiments. The definitive screening design (DSD) was then utilized to screen and optimize these parameters. Stepwise regression was applied to establish quantitative models between the critical method attributes and the method parameters. Subsequently, the method operable design region (MODR) was calculated and was successfully verified. The analytical conditions established were configured with 0.1% formic acid in water and 0.1% formic acid in acetonitrile serving as the mobile phases. The flow rate was set at 0.8 mL/min, and the column temperature was maintained at 35 °C with the evaporation tube temperature also set at 35 °C. An injection volume of 10 μL was used for each analysis. The gradient elution conditions were as follows: from 0 to 30 min, 75% of solvent B was used, and from 30 to 60 min, the proportion of solvent B was increased from 75% to 79%. Ten components, including 12-hydroxystearic acid, 2-hexyldecanoic acid, and palmitic acid, were identified by mass spectrometry, and seven common peaks were found in the fingerprints. The contents of palmitic acid, oleic acid, and stearic acid in the crude lanolin were quantitatively determined. Both the fingerprint and quantitative analysis methods were validated. The method was applied to analyze 15 batches of crude lanolin from different sources. The new established quantitative profiling method for free fatty acids can be potentially used for industrial applications to enhance the quality control of crude lanolin. Full article
(This article belongs to the Special Issue Spectroscopic Techniques for Chemical Analysis)
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5 pages, 493 KiB  
Proceeding Paper
Isolation and Characterization of Two Coumarin Compounds from the Chloroform Fraction of Scadoxus multiflorus (Martyn) Raf. (Amaryllidaceae)
by Olaiya Akeem Ayodele, Tijani Tawakaltu Omolara, Abdullahi Sakynah Musa and Sule Mohammed Ibrahim
Chem. Proc. 2024, 16(1), 89; https://doi.org/10.3390/ecsoc-28-20184 - 18 Feb 2025
Viewed by 735
Abstract
In this study, the aerial parts of Scadoxus multiflorus were extracted using methanol through a maceration process. The resulting methanol crude extract was subsequently partitioned with solvents including n-hexane, chloroform, ethyl acetate, and n-butanol. Extensive column chromatography separation of the chloroform fraction, followed [...] Read more.
In this study, the aerial parts of Scadoxus multiflorus were extracted using methanol through a maceration process. The resulting methanol crude extract was subsequently partitioned with solvents including n-hexane, chloroform, ethyl acetate, and n-butanol. Extensive column chromatography separation of the chloroform fraction, followed by isocratic elution of two pooled fractions, led to the isolation of two coumarin derivatives: 2-methyl-2H-chromen-7-ol and 7-methoxy-2H-chromen-2-one. These compounds underwent various physicochemical analyses, such as chemical tests, melting point determination, and solubility assessments. Structural elucidation of the isolated compounds was conducted using UV spectroscopy, FT-IR, and 1D/2D NMR techniques. The final molecular structures were confirmed and named using ChemDraw. Full article
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13 pages, 1533 KiB  
Article
Protocol for the Determination of Total Iodine in Iodized Table Salts Using Ultra-High-Performance Liquid Chromatography
by Mohd Azerulazree Jamilan, Aswir Abd Rashed and Mohd Fairulnizal Md Noh
Chemosensors 2025, 13(2), 46; https://doi.org/10.3390/chemosensors13020046 - 3 Feb 2025
Cited by 2 | Viewed by 1388
Abstract
Potassium iodate and potassium iodide are commonly fortified in iodized table salt, which must be continuously monitored to maintain quality. Our study reported an optimized detection method for total iodine in iodized table salt using 0.5 M sodium bisulfite as the reducing agent. [...] Read more.
Potassium iodate and potassium iodide are commonly fortified in iodized table salt, which must be continuously monitored to maintain quality. Our study reported an optimized detection method for total iodine in iodized table salt using 0.5 M sodium bisulfite as the reducing agent. The iodized table salt (0.5 g) was dissolved in 0.5 M sodium bisulfite solution prior to injection in ultra-high-performance liquid chromatography (UHPLC) coupled with a diode array detector using a weak anion-exchange column (2.1 mm × 150 mm, 5 μm). Iodide was eluted at 9.92 ± 0.06 min (λ = 223 nm) when an isocratic mobile phase of 1:1 (v/v) methanol/120 mM phosphate buffer mixed with tetrasodium pyrophosphate (pH 3.0) was running at 0.20 mL/min (15 min). Iodide was detected as total iodine from 10.0 to 50.0 mg/kg with a limit of detection (LOD) of 1.2 mg/kg and a limit of quantification (LOQ) of 3.7 mg/kg. The method was validated with relative standard deviations (RSDs) of 4.2%, 0.4%, 1.6%, and 0.8% for accuracy, repeatability, intermediate precision, and robustness, respectively. The determination of total iodine was successful on six (6) samples (n = 3), which recovered 87.2–106.9% of iodate and iodide spike. Thus, this study provides a validated protocol for the determination of total iodine in iodized table salt using 0.5 M sodium bisulfite. Full article
(This article belongs to the Special Issue Green Analytical Chemistry: Current Trends and Future Developments)
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19 pages, 2632 KiB  
Article
A Novel Mobile Phase for Green Chromatographic Determination of Haloperidol: Application to Commercial Pharmaceutical Products and Forced Degradation Studies
by Khadidja Djilali, Rachida Maachi, Mohammed Danish, Sabrina Lekmine, Mohamed Hadjadj, Zohra Ait Mesbah, Ouided Benslama, Hichem Tahraoui, Mohammad Shamsul Ola, Ahmad Ali, Jie Zhang and Abdeltif Amrane
Processes 2025, 13(1), 260; https://doi.org/10.3390/pr13010260 - 17 Jan 2025
Cited by 3 | Viewed by 1217
Abstract
The target molecule of this study is haloperidol, a neuroleptic from the butyrophenone family. It is one of the most widely used psychotropic drugs globally and is considered as effective as other low-potency psychotropic medications. The RP-HPLC method employed in this study utilizes [...] Read more.
The target molecule of this study is haloperidol, a neuroleptic from the butyrophenone family. It is one of the most widely used psychotropic drugs globally and is considered as effective as other low-potency psychotropic medications. The RP-HPLC method employed in this study utilizes a novel mobile phase composed of a 90:10 mixture of methanol and phosphate buffer (pH = 9.8) for isocratic elution. This method has been validated with a correlation coefficient (R) of 0.999 across a concentration range of 2.5 to 50 µg/mL. It exhibits excellent sensitivity, with a relative standard deviation (RSD) of less than 2% for both precision and accuracy. The method is highly effective for the analysis of haloperidol in oral commercial formulations. The mobile phase is cost-efficient, environmentally friendly, and simple to use, making it suitable for analyzing haloperidol in both liquid and powder forms. Additionally, the method is applied to monitor haloperidol degradation under various stress conditions. For powder samples, the maximum degradation observed was 6.20% after 48 h of sunlight exposure. For liquid haloperidol samples, stability was retained only under oxidative stress conditions, with the highest degradation (57.36%) occurring after 48 h of sunlight exposure and the lowest degradation (10.03%) observed under thermal stress at 60 °C over seven days. Full article
(This article belongs to the Section Pharmaceutical Processes)
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19 pages, 2205 KiB  
Article
An Ultra-Fast Validated Green UPLC-MS/MS Approach for Assessing Revumenib in Human Liver Microsomes: In Vitro Absorption, Distribution, Metabolism, and Excretion and Metabolic Stability Evaluation
by Mohamed W. Attwa, Ali S. Abdelhameed and Adnan A. Kadi
Medicina 2024, 60(12), 1914; https://doi.org/10.3390/medicina60121914 - 21 Nov 2024
Cited by 7 | Viewed by 1408
Abstract
Background and Objectives: Revumenib (SNDX-5613) is a powerful and specific inhibitor of the menin–KMT2A binding interaction. It is a small molecule that is currently being researched to treat KMT2A-rearranged (KMT2Ar) acute leukemias. Revumenib (RVB) has received Orphan Drug Designation from the US FDA [...] Read more.
Background and Objectives: Revumenib (SNDX-5613) is a powerful and specific inhibitor of the menin–KMT2A binding interaction. It is a small molecule that is currently being researched to treat KMT2A-rearranged (KMT2Ar) acute leukemias. Revumenib (RVB) has received Orphan Drug Designation from the US FDA for treating patients with AML. It has also been granted Fast Track designation by the FDA for treating pediatric and adult patients with R/R acute leukemias that have a KMT2Ar or NPM1 mutation. Materials and Methods: The target of this research was to create a fast, precise, green, and extremely sensitive UPLC-MS/MS technique for the estimation of the RVB level in human liver microsomes (HLMs), employing an ESI source. The validation procedures were carried out in accordance with the bioanalytical technique validation requirements established by the US Food and Drug Administration that involve linearity, selectivity, precision, accuracy, stability, matrix effect, and extraction recovery. The outcome data of the validation features of the UPLC-MS/MS approach were acceptable according to FDA guidelines. RVB parent ions were formed in the positive ESI source and its two fragment ions were estimated employing multiple reaction monitoring (MRM) mode. The separation of RVB and encorafenib was achieved using a C8 column (2.1 mm, 50 mm, and 3.5 µm) and isocratic mobile phase. Results: The RVB calibration curve linearity ranged from 1 to 3000 ng/mL (y = 0.6515x − 0.5459 and R2 = 0.9945). The inter-day precision and accuracy spanned from −0.23% to 11.33%, while the intra-day precision and accuracy spanned from −0.88% to 11.67%, verifying the reproducibility of the UPLC-MS/MS analytical technique. The sensitivity of the developed methodology demonstrated its capability to quantify RVB levels at an LOQ of 0.96 ng/mL. The AGREE score was 0.77, confirming the greenness of the current method. The low in vitro t1/2 (14.93 min) and high intrinsic clearance (54.31 mL/min/kg) of RVB revealed that RVB shares similarities with medications that have a high extraction ratio. Conclusions: The present LC-MS/MS approach is considered the first analytical approach with the application of metabolic stability assessment for RVB estimation in HLMs. These methods are essential for advancing the development of new pharmaceuticals, particularly in enhancing metabolic stability. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia: Update on Diagnosis, Therapy, and Monitoring)
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5 pages, 748 KiB  
Proceeding Paper
Development and Validation of the Stability of p-SCN-Bn-Df via the Reversed-Phase Chromatography Method: Practical Experiences
by Anjli Shrivastav, Mohd. Faheem, Vaibhav Pandey and Manish Dixit
Chem. Proc. 2024, 16(1), 39; https://doi.org/10.3390/ecsoc-28-20175 - 14 Nov 2024
Viewed by 425
Abstract
The DFO, a special hexadentate chelator with three hydroxamate moieties, is a bifunctional 1-(4-isothiocyanatophenyl)-3-[6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)- 6,11,17, 22- tetraazaheptaeicosine] thiourea (p-SCN-Bn-Df), a significant next-generation ligand. The presence of the thiocyanate (-SCN) group makes it capable of hydrolysis and the protonation process. In this study aims [...] Read more.
The DFO, a special hexadentate chelator with three hydroxamate moieties, is a bifunctional 1-(4-isothiocyanatophenyl)-3-[6,17-dihydroxy-7,10,18,21-tetraoxo-27-(N-acetylhydroxylamino)- 6,11,17, 22- tetraazaheptaeicosine] thiourea (p-SCN-Bn-Df), a significant next-generation ligand. The presence of the thiocyanate (-SCN) group makes it capable of hydrolysis and the protonation process. In this study aims to optimize the HPLC protocol for 1-(4-isothiocyanatophenyl)-3-[6,17-dihydroxy-7,10,18,21-tetraoxo-27-(n-acetylhydroxylamino)-6,11,17,22-tetraazaheptaeicosine] thiourea (p-SCN-Bn-Df) via the Reversed-Phase Chromatography (RP-HPLC) method. A variety of mobile phases were tested in various ratios of solvent constituents such as methanol/water, acetonitrile/water, and phosphate buffer along with at variable pH concentrations. However, when employing a mobile phase consisting of water to acetonitrile containing 0.1% TFA (05:95, v/v) in an isocratic manner, satisfactory separation and symmetric peaks were observed. This method utilized an Eclipsed C-18 column (5 μm, 4.6 × 250 mm) column with a flow rate of 0.5 mL/min. The maximum absorption of p-SCN-Bn-Dfat 254 nm wavelength was selected as the detection wavelength. The Retention time (tR) of p-SCN-Bn-Df was found at 5.205 min. The ICH guideline was used to evaluate the linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), specificity, and system appropriateness criteria to validate the optimized chromatographic and spectrophotometric procedures. For accurate compound separation in pharmaceutical and environmental analyses, this phase is adaptable and often used. This study is useful for the evaluation of p-SCN-Bn-Df QC parameters and chelation rates with different radioisotopes e.g., Zirconuim-89 (Zr-89). Full article
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6 pages, 1147 KiB  
Proceeding Paper
Hydro-Lipophilic Properties of Chlorinated and Brominated 1-Hydroxynaphthalene-2-Carboxanilides
by Lucia Vrablova, Tomas Gonec and Josef Jampilek
Chem. Proc. 2024, 16(1), 26; https://doi.org/10.3390/ecsoc-28-20151 - 14 Nov 2024
Viewed by 498
Abstract
1-Hydroxy-N-phenylnaphthalene-2-carboxamide and a series of seventeen other carboxanilides in the anilide part of dichlorinated, trichlorinated, dibrominated, tribrominated, and chlorinated/brominated variants have recently been reported as biologically active compounds mainly with antibacterial, antimycobacterial, and anticancer effects. Since lipophilicity is one of the [...] Read more.
1-Hydroxy-N-phenylnaphthalene-2-carboxamide and a series of seventeen other carboxanilides in the anilide part of dichlorinated, trichlorinated, dibrominated, tribrominated, and chlorinated/brominated variants have recently been reported as biologically active compounds mainly with antibacterial, antimycobacterial, and anticancer effects. Since lipophilicity is one of the factors influencing the bioavailability (absorption, distribution, metabolism, and elimination), activity, and even toxicity of bioactive compounds, all the derivatives were investigated for their lipophilic and hydrophilic properties. All eighteen compounds were analyzed by reversed-phase high-performance liquid chromatography (RP-HPLC). The procedure was performed under isocratic conditions with methanol as the organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. The lipophilicity values are expressed as the logarithm of the capacity factor k (for the mobile phase water/methanol) and the distribution coefficients D at pH values of 6.5 and 7.4 (for the mobile phase buffer/methanol), as well as the calculated values of log P/Clog P by various methods. 1-Hydroxy-N-(3,4,5-trichlorophenyl)naphtha- lene-2-carboxamide and N-(4-bromo-3-chlorophenyl)-1-hydroxynaphthalene-2-carboxamide are the most lipophilic compounds of the whole series; on the other hand, surprisingly, unsubstituted 1-hydroxy-N-phenylnaphthalene-2-carboxamide is not the least lipophilic derivative. The mutual correlations between the experimental and predicted lipophilicity values are low; in addition, there are large deviations in the cross-correlations between log k and log D, which are due to the presence of a free ionizable phenolic group in the molecule. Full article
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