Journal of Pharmaceutical and Biomedical Analysis Open最新文献

{"title":"Studies on the thermal behavior of sildenafil citrate","authors":"Francisco V.B. Nascimento,&nbsp;Ana P.G. Ferreira,&nbsp;Rafael T. Alarcon,&nbsp;Éder T.G. Cavalheiro","doi":"10.1016/j.jpbao.2024.100028","DOIUrl":"https://doi.org/10.1016/j.jpbao.2024.100028","url":null,"abstract":"<div><p>Thermal behavior of sildenafil citrate (SC), a vasodilator used in the treatment of both erectile dysfunction (ED) and pulmonary arterial hypertension (PAH) treatment was investigated by thermogravimetry-differential thermal analysis (TGA-DTA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and evolved gas analysis by thermogravimetry coupled to infrared spectroscopy (TGA-FTIR). Under N₂ and air atmospheres SC remained thermally stable until 180.0 °C, and then decomposed in three steps under N₂ and four steps under air. DSC curves showed two endothermic events at first heating, one related to the dehydration around 63.5 °C and the second event is a concomitant melting-decomposition process (T_{<em>peak</em>} = 199.6 °C). Cold recrystallization was observed during the second heating, with peaks at 119.8 °C and 129.7 °C and melting at 179.7 °C. XRD results for powder collected at 138 °C suggested that the phase formed is the sildenafil free base. TGA-FTIR revealed that the thermal decomposition of SC initiates with release of water, carbon dioxide, and itaconic anhydride, resulting from the decomposition of the citrate counter-ion. Above 303 °C, CO, SO₂, benzene, ethanol, 1-methylpiperazine, isocyanic acid, and methylamine were identified in the gas phase. Based on these results, a thermal behavior mechanism for sildenafil citrate was proposed.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"3 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X24000045/pdfft?md5=134e435dc2a8a6224a704fbdbde2b6aa&pid=1-s2.0-S2949771X24000045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140539168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating matrix effects for LC-MS/MS quantification of nitrosamine impurities in rifampin and rifapentine","authors":"Qiyao Li ,&nbsp;Qun Xu ,&nbsp;Nadine Lo ,&nbsp;Allan T. Leeks Jr. ,&nbsp;Mark Han ,&nbsp;Marcela Nefliu ,&nbsp;John T. Simpson ,&nbsp;Jennifer L. Belsky","doi":"10.1016/j.jpbao.2024.100027","DOIUrl":"https://doi.org/10.1016/j.jpbao.2024.100027","url":null,"abstract":"<div><p>Since the discovery of potentially mutagenic nitrosamine impurities in pharmaceuticals in 2018, liquid chromatography-mass spectrometry (LC-MS) methods have been widely applied for the trace level quantification of nitrosamines. As more nitrosamines and drug samples are analyzed, method accuracy is increasingly recognized as a major analytical challenge. Matrix effects can have a significant adverse impact on method accuracy but have not attracted much attention in nitrosamine quantification literature. In this study, we observed severe matrix effects when adapting LC-MS method conditions from a published and validated method for the analysis of nitrosamines in tuberculosis drugs. Several approaches were explored to mitigate these matrix effects, including using stable isotope-labeled internal standards, modifying LC conditions and sample concentration, and quantifying with standard addition instead of an external calibration method. The results underscore the importance of monitoring matrix effects and validating nitrosamine quantification procedures for specific sample matrices. Finally, two LC-MS/MS methods are presented with validation data for the quantification of 1-methyl-4-nitrosopiperazine (MNP) in rifampin and 1-cyclopentyl-4-nitrosopiperazine (CPNP) in rifapentine and revealed high nitrosamine levels in the tested samples that far exceeded recommended acceptable intake limits.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"3 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X24000033/pdfft?md5=943d4b0163ce944a7c98d3f4e92c1d2d&pid=1-s2.0-S2949771X24000033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139987016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of biowaste-derived nanostructured material for the nanomolar detection of glucose: Biological sample analysis","authors":"Shweta J. Malode ,&nbsp;Shireesha Bilagi ,&nbsp;Nagaraj P. Shetti","doi":"10.1016/j.jpbao.2024.100026","DOIUrl":"https://doi.org/10.1016/j.jpbao.2024.100026","url":null,"abstract":"<div><p>Glucose electro-oxidation in an alkaline media was investigated using an electrode composed of carbon paste and sugarcane bagasse activated carbon (SBAC). The SBAC was prepared using an easy, affordable, and environmental friendly process. The porous activated carbon was produced using sugarcane bagasse through a pre-treatment process that involved carbonization at 650 °C and K₂CO₃. X-ray diffraction (XRD) was used to observe the formation of carbon crystallites during activation at higher temperatures. The Fourier-transform infrared (FTIR) spectrum shows functional groups that are present in the carbon material. The carbon sample's morphology was evaluated using scanning electron microscope (SEM). The surface roughness was studied using atomic force microscopy (AFM). Porous activated carbon derived from sugarcane bagasse was carefully mixed into electrode components such as graphite powder and mineral oil for glucose (GLS) detection. For precise GLS detection, the SBACs were employed as non-enzymatic electrochemical sensor probes in their as-prepared condition. According to the electrochemical experiments, the constructed sensor shows exceptional electrochemical performance towards glucose oxidation, including excellent selectivity, a low detection limit, good sensitivity, and a wide linear range. Investigation has been conducted on the oxidation of GLS in alkaline solutions with varying concentrations of halide ions such as iodide and chloride. The GLS oxidation peak current increased the performance of a SBAC modified electrode was compared to that of a bare carbon paste electrode (CPE). The role of sensitivity in minimizing halide poisoning is significant. The risk of poisoning is increased if iodide &gt; chloride. As the modified electrode's voltage changes in a chloride solution containing glucose, the peak current gradually reduces. The redesigned electrode that is currently in use as a consequence not only promotes glucose oxidation but also shows strong resistance to electrode poisoning caused by halides. The sensitive and targeted SBAC/CPE has also improved its reliability while evaluating samples of human serum, urine, and breast milk.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"3 ","pages":"Article 100026"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X24000021/pdfft?md5=5af6905d7f946aac73c3319cc9e20fb4&pid=1-s2.0-S2949771X24000021-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139987015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a sensitive bioanalytical method for metronidazole extraction from human plasma","authors":"Krishna Kumar Patel ,&nbsp;Valeria Cota ,&nbsp;Nicole K. Brogden","doi":"10.1016/j.jpbao.2024.100025","DOIUrl":"https://doi.org/10.1016/j.jpbao.2024.100025","url":null,"abstract":"<div><p>Metronidazole (MTZ) is a broad-spectrum antibiotic with numerous routes of administration, including topical. Topical application of MTZ gel or cream results in very low systemic absorption, resulting in the need for a sensitive extraction method to quantify plasma concentrations. Currently published methods are not suitable for analysis of plasma concentrations after topical application, as undetectable MTZ concentrations commonly occur. We validated a simple extraction method for MTZ recovery from plasma and quantified it using an LC-MS/MS analytical method. Methods: Plasma samples were spiked with MTZ (0.5 – 5 ng/mL) and internal standard (tinidazole, 2 ng/mL). MTZ was extracted by liquid-liquid extraction using ethyl acetate and acetonitrile mixture (4:1) as the extraction solvent. A quadrupole mass spectrometer interfaced with an Acquity H-Class HPLC was used to quantify MTZ concentrations in positive ion mode. A Kinetix C18 analytical column (150 mm × 4.6 mm i.d., 5 µm particle size) was used for separation. The plasma extraction method was validated for various parameters, including % recovery, precision, accuracy, and stability. Results: The extraction method demonstrated high MTZ recovery, ranging from 93.7 – 97.5%. The calibration curve prepared using MTZ samples extracted from plasma (0.5 – 5 ng/mL) had excellent linearity with R² = 0.999. The extracted samples also showed higher autosampler and freeze-thaw stability over a 72-hr period. The mean intra- and inter-day accuracy and precision of the extraction assay ranged from 97 to 101.6% and 2.7 – 4.8% RSD, respectively. The assay was highly efficient, with a limit of quantification (0.53 ± 0.04 ng/mL) lower than previously published methods (≥5 ng/mL). The extraction method was successfully validated using LC-MS/MS and can be used to extract and detect trace amounts of MTZ in plasma after topical application.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"3 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X2400001X/pdfft?md5=9b688a9f3a812c65521b6f8b3ea5aeb2&pid=1-s2.0-S2949771X2400001X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative physicochemical and biological characterization of the similar imiglucerase product Glurazyme® and the originator product Cerezyme®","authors":"Maksim Smolov,&nbsp;Serge Taran,&nbsp;Ivan Lyagoskin,&nbsp;Maria Neronova,&nbsp;Maksim Degterev,&nbsp;Rakhim Shukurov","doi":"10.1016/j.jpbao.2023.100024","DOIUrl":"10.1016/j.jpbao.2023.100024","url":null,"abstract":"<div><p>A biosimilar considered as a biomolecule medicinal product that is comparable to a reference medicinal product in terms of the structural, functional, biological, and clinical attributes. Glurazyme® was developed as a biosimilar to Cerezyme® (imiglucerase) and was approved in CIS countries (Russian Federation, Belarus, Kazakhstan) and recently Algeria for the treatment of type 1 and type 3 Gaucher disease. The quality assessment of Glurazyme® was performed in accordance with the Rules for the Study of Biological Medicines of the Eurasian Economic Union harmonized with the ICH comparability guideline and the biosimilar guidelines of the European Medicines Agency and Food and Drug Administration. Extensive side-by-side comparison was employed with state-of-the-art and orthogonal assays designed to interrogate all expected physicochemical and biological activities, including those known to affect the mechanisms of action for imiglucerase. Similarity evaluation was performed on the basis of tolerance intervals determined from about 10 lots of commercial Cerezyme®. Mainly three discrepancies of quality attributes were established concerning oxidized and deamidated forms as well as phosphorylated oligomannose N-glycans reflecting the difference between cultivation and down-stream processes of both medicinal products. Nevertheless, all of them possess a little or no influence on safety and efficacy.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"3 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X23000245/pdfft?md5=af72c4a69d296aaef6a235848c9bb9e1&pid=1-s2.0-S2949771X23000245-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139014105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to determine residual aldehyde content in conjugated polysaccharides with 3-methyl-2-benzothiazolinonehydrazon (MBTH) by colorimetric method, automation, and HP-SEC","authors":"Weidong Tong,&nbsp;Mingxiang Lin,&nbsp;Ping Zhuang,&nbsp;Bukuru Anaclet,&nbsp;Castle Cooper","doi":"10.1016/j.jpbao.2023.100022","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100022","url":null,"abstract":"<div><p>Polysaccharide activation by periodate oxidation to form aldehydes, followed by conjugation with proteins via reductive amination is a general procedure to make polysaccharide-protein conjugate vaccines. Controlling the level of residue aldehyde content after conjugation is critical to ensure vaccine product stability. Herein, to support conjugation process optimization, we developed a 3-methyl-2-benzothiazolone hydrazone (MBTH) chemistry-based colorimetric method, which can measure low-level residual aldehyde polysaccharide-protein conjugate in high throughput 96-well plate format. This mechanism of detection works in two steps. First, MBTH reacts with the aldehyde group to form azine. Then the excess MBTH was oxidized by ferric ammonium sulfate in sulfamic acid to form a reactive cation, which reacts further with azine to form formazan, a characteristic blue chromophore at 610 nm, for colorimetric detection. The method performance, including detection limit, linearity range, matrix effect, kinetics, and color stability was systematically studied. For samples with severe matrix interference, a supplemental size exclusion chromatography (SEC) method was also developed as an alternative method.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X23000221/pdfft?md5=eafa9469ba2f3683e089c099514af195&pid=1-s2.0-S2949771X23000221-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136968400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a LC–MS/MS analytical method of 15 compounds related to renal function for a prognostic method of progression risk in patients with diabetic kidney disease","authors":"Ryota Kujirai ,&nbsp;Yotaro Matsumoto ,&nbsp;Mizuki Abe ,&nbsp;Kodai Hiramoto ,&nbsp;Takumi Watanabe ,&nbsp;Chitose Suzuki ,&nbsp;Takafumi Toyohara ,&nbsp;Takaaki Abe ,&nbsp;Yoshihisa Tomioka","doi":"10.1016/j.jpbao.2023.100021","DOIUrl":"10.1016/j.jpbao.2023.100021","url":null,"abstract":"<div><p>Diabetic kidney disease (DKD) onset and progression is a major cause of end-stage renal failure in diabetic patients, however, no practical method has been reported to predict the progression rate of renal function decline. Nine serum compounds are reported to associate with prognosis in type 1 diabetes patients; however, quantitative analytical methods for these compounds lacks. Herein, we developed a simultaneous quantitative method for 15 compounds, including Niewczas’s nine biomarker candidates, associated with renal function and its prognosis in kidney disease patients to achieve a prognostic method of renal function decline in DKD patients. This report describes the development and validation of a LC–MS/MS analytical method for 15 compounds of biomarker candidates using human plasma, serum, and urine as sample matrices. The analytes are N-acetyl-L-alanine, N6-acetyl-L-lysine, N-acetyl-L-serine, N-acetyl-L-threonine, phenyl sulfate, pseudouridine, N6-threonylcarbamoyladenosine, tryptophan 2-C-mannoside, tyrosine O-sulfate, creatinine, p-cresol sulfate, 4-ethylphenyl sulfate, indoxyl sulfate, N1-methyladenosine, and trimethylamine N-oxide. The Capcell Pak ADME-HR column was compared to several general columns and selected as the most suitable column for the simultaneous analysis of all 15 compounds. The proposed method was validated for selectivity, accuracy, precision, stability, dilution integrity, and parallelism. This report describes the suitability of the calibration ranges established and the actual sample concentrations of serum and urine from type 2 diabetic patients, as well as new findings on the unknown analyte levels of several compounds in these samples. The proposed method can be used to aid the development of prognostic methods for renal function decline in patients with DKD.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X2300021X/pdfft?md5=f0b7f3218761bed3d45465c43370fd8d&pid=1-s2.0-S2949771X2300021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135371227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formic acid-aided sample preparation method for sensitive and simultaneous analysis of eight nitrosamines in poorly-water soluble pharmaceutical drugs using liquid chromatography–ultraviolet detection","authors":"Eiichi Yamamoto,&nbsp;Hitomi Kan-no,&nbsp;Daisuke Ando,&nbsp;Tamaki Miyazaki,&nbsp;Tatsuo Koide,&nbsp;Ken-ichi Izutsu,&nbsp;Yoji Sato","doi":"10.1016/j.jpbao.2023.100020","DOIUrl":"10.1016/j.jpbao.2023.100020","url":null,"abstract":"<div><p>There has been a growing concern over the contamination of pharmaceutical products with nitrosamines (NAs) such as <em>N</em>-nitrosodimethylamine (NDMA). To quantify NA levels in drugs using reversed-phase liquid chromatography (LC), the sample solution should achieve a high drug concentration to detect trace NAs, and an appropriate amount of hydrophilic NAs should be retained. However, these are difficult to achieve, and no suitable method has yet been developed. The present study was the first to develop a sample preparation method to achieve this by combining drugs with formic acid (FA), followed by the removal of active pharmaceutical ingredients (APIs) from samples via crystallization. This method was successfully applied for the sensitive quantification of eight NAs in poorly water-soluble acidic atorvastatin (ATS) and basic itraconazole (ITC) via LC–ultraviolet (LC-UV) detection. The removal rate of ITC via recrystallization exceeded 99.96 %, whereas most NAs remained as solutes. Assuming that the enhancement in ITC solubility directly translates to heightened analytical sensitivity, a &gt; 100-fold increase in sensitivity was attained compared to conventional methodologies. This sample preparation method would be applicable to other poorly water-soluble drugs, contributing to the control of NA content in various formulations to realize the safe delivery of pharmaceuticals to patients.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X23000208/pdfft?md5=7d42ede05957e2e87dab21117535373b&pid=1-s2.0-S2949771X23000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135965851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in surface plasmon resonance biosensors for medical diagnostics: An overview of recent developments and techniques","authors":"G.I. Janith ,&nbsp;H.S. Herath ,&nbsp;N. Hendeniya ,&nbsp;D. Attygalle ,&nbsp;D.A.S. Amarasinghe ,&nbsp;V. Logeeshan ,&nbsp;P.M.T.B. Wickramasinghe ,&nbsp;Y.S. Wijayasinghe","doi":"10.1016/j.jpbao.2023.100019","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100019","url":null,"abstract":"<div><p>Over the last two decades, surface plasmon resonance (SPR) sensors have advanced significantly, becoming an important tool in disciplines such as biosensing, chemical sensing, and material characterization. SPR has gained popularity in biosensing because of its great sensitivity and specificity in detecting biomolecular interactions. This review provides an overview of the recent developments of the SPR biosensor technology and its applications in medical diagnostics. To provide an up-to-date overview of the area, the review includes the most recent works from the last decade. Furthermore, it explores various configurations (prism, grating, fiber optic, waveguide modulated) and wave properties (angle, wavelength, phase) being tracked for sensing together with strategies for enhancing sensitivity and selectivity through mechanisms such as surface coatings, sensing mediums, and immobilization techniques.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49879898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of UHPLC-ESI-MS/MS bioanalytical method, ADMET profiling, and pharmacokinetic study of bioactive phytoconstituents from Ayurvedic botanical Guduchi (Tinospora cordifolia)","authors":"Aboli Girme,&nbsp;Vijay Parmar,&nbsp;Shubham Jagtap,&nbsp;Ganesh Saste,&nbsp;Siddharth J. Modi,&nbsp;Lal Hingorani","doi":"10.1016/j.jpbao.2023.100018","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100018","url":null,"abstract":"<div><p><em>Tinospora cordifolia</em> (TC) is known for its immense therapeutic applications in 'Ayurveda', which has created considerable scientific interest in pharmacology. Thus, a targeted and rapid bioanalytical UHPLC-ESI-MS/MS method was developed and validated for the extraction of its bioactive markers from diverse classes of diterpenes as tinosporide (TC1) and phytosterol-20-β-hydroxyecdysone (TC2) and isoquinoline alkaloids-jatrorrhizine (TC3), tetrahydropalmatine (TC4) from the TC stem extract (TCE) in rat plasma by solid phase extraction technique (SPE). The optimum recovery (≥ 90 %) was achieved for TC1–4 and internal standard fluoxymesterone (IS) with the SPE method on the C18 phase. The analytes were subjected to chromatographic analysis on the Agilent C18 Zorbax Eclipse Plus column (4.6 × 100 mm, 3.5 µ) with a gradient program using 0.1 % acetic acid in water (% <em>v/v</em>) and acetonitrile as mobile phase at a flow rate of 0.500 mL/min. The MS/MS quantification and validation were performed on the Shimadzu 8045 tandem mass spectrometer associated with the heated-ESI probe in SRM mode. The precursor to product ion transitions <em>m/z</em> 416.20→375.10 (TC1), 481.40→445.20 (TC2), 339.15→323.05 (TC3), 356.25→192.10 (TC4) and 337.20→91.00 (IS) were used for quantification. Also, <em>in silico</em> ADMET prediction and <em>in vivo</em> pharmacokinetics revealed that TC1–4 was well absorbed from the GI tract and could act as a P-GP substrate. In the pharmacokinetic study<em>,</em> TC1–4 could be detected by this validated bioanalytical method. The TC1 was found bioavailable, having an optimum half-life of &gt; 9.0 h to exhibit therapeutic activity with other TC bioactive markers <em>in vivo</em>. This research is the first comprehensive study on <em>in silico</em> and <em>in vivo</em> pharmacokinetics of TC biomarkers, which may aid in further pre-clinical and clinical trial investigations.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49879899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}