Objective:: This study aimed to establish a simple, reliable, and sensitive method for detecting ketamine, fluoroketamine, and their metabolites in urine using UPLC-MS/MS. Methods:: The chromatographic separation was performed on UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) at a column temperature of 40°C. The mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile, with a flow rate set at 0.4 mL/min, following a specific elution procedure. A urine sample was treated with acetonitrile, and midazolam was used as an internal standard. Multiple reaction monitoring was used for quantitative analysis. Results:: Ketamine, fluoroketamine, norketamine, and 2-norfluoro-ketamine exhibited linearity in urine (r>0.99) within the concentration range of 5–2000 ng/mL. Intra-day and inter-day precisions were 9% or less and 12% or less, respectively. The accuracy ranged from 92 to 107%. Mean recoveries were above 76%. The measured matrix effect was between 85 and 104%. Conclusion:: This simple, reliable, and sensitive PLC-MS/MS method was successfully developed to determine ketamine, fluoroketamine, and their metabolite in rat urine.
{"title":"Determination of Ketamine, Fluoroketamine, Norketamine, and 2-Norfluoro-ketamine in Urine Using Ultra-performance Liquid Chromatography-tandem Mass Spectrometry","authors":"Meiling Zhang, Xicheng Dong, Wanhang Wang, Ziyue Wang, Dizhong Chen, Congcong Wen, Xianqin Wang","doi":"10.2174/0115734129280521240110094134","DOIUrl":"https://doi.org/10.2174/0115734129280521240110094134","url":null,"abstract":"Objective:: This study aimed to establish a simple, reliable, and sensitive method for detecting ketamine, fluoroketamine, and their metabolites in urine using UPLC-MS/MS. Methods:: The chromatographic separation was performed on UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) at a column temperature of 40°C. The mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile, with a flow rate set at 0.4 mL/min, following a specific elution procedure. A urine sample was treated with acetonitrile, and midazolam was used as an internal standard. Multiple reaction monitoring was used for quantitative analysis. Results:: Ketamine, fluoroketamine, norketamine, and 2-norfluoro-ketamine exhibited linearity in urine (r>0.99) within the concentration range of 5–2000 ng/mL. Intra-day and inter-day precisions were 9% or less and 12% or less, respectively. The accuracy ranged from 92 to 107%. Mean recoveries were above 76%. The measured matrix effect was between 85 and 104%. Conclusion:: This simple, reliable, and sensitive PLC-MS/MS method was successfully developed to determine ketamine, fluoroketamine, and their metabolite in rat urine.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"4 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139579335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-26DOI: 10.2174/0115734129286029240106123114
Amitava Kabiraj, Rohitas Deshmukh
Introduction:: Indigestion leading to Flatulence is a common problem for infants, and tackling it is tedious for the parents. So, addressing the issue with an ideal formulation should likely have a combination of digestive enzymes and carminatives. Method:: A formulation containing enzymes like Fungal Diastase (Amylase) and Papain (Protease) for the digestion of Carbohydrates and Protein, respectively, along with aromatic, volatile, carminative oils like Dill Oil, Anise Oil, and Caraway Oil can serve the purpose to mitigate problems associated with infant indigestion and flatulence with maximum compliance. Result:: The stability of multi-enzyme and analysis of carminative oil mixtures still need to be improved due to their inherent characteristics. Enzymes are very likely susceptible to changes in temperature and pH, while the solubility of carminative oils is minimal in the aqueous phase. Also, each enzyme is stable in different pH ranges. Nine emulsions were developed using a suitable buffer system and analyzed by HPLC method. Conclusion:: The optimum pH range was found, and analytical method validation was done for the method's accuracy, precision, and repeatability. The optimum pH was 6-6.5, and the active pharmaceutical ingredients (API) assay was found within the acceptable limit of NLT, 90% for enzymes and 90-110% for carminative oils.
{"title":"Formulation, Analytical Method Development and Validation of an Emulsion of Multi-Enzyme with Carminative Oils","authors":"Amitava Kabiraj, Rohitas Deshmukh","doi":"10.2174/0115734129286029240106123114","DOIUrl":"https://doi.org/10.2174/0115734129286029240106123114","url":null,"abstract":"Introduction:: Indigestion leading to Flatulence is a common problem for infants, and tackling it is tedious for the parents. So, addressing the issue with an ideal formulation should likely have a combination of digestive enzymes and carminatives. Method:: A formulation containing enzymes like Fungal Diastase (Amylase) and Papain (Protease) for the digestion of Carbohydrates and Protein, respectively, along with aromatic, volatile, carminative oils like Dill Oil, Anise Oil, and Caraway Oil can serve the purpose to mitigate problems associated with infant indigestion and flatulence with maximum compliance. Result:: The stability of multi-enzyme and analysis of carminative oil mixtures still need to be improved due to their inherent characteristics. Enzymes are very likely susceptible to changes in temperature and pH, while the solubility of carminative oils is minimal in the aqueous phase. Also, each enzyme is stable in different pH ranges. Nine emulsions were developed using a suitable buffer system and analyzed by HPLC method. Conclusion:: The optimum pH range was found, and analytical method validation was done for the method's accuracy, precision, and repeatability. The optimum pH was 6-6.5, and the active pharmaceutical ingredients (API) assay was found within the acceptable limit of NLT, 90% for enzymes and 90-110% for carminative oils.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"4 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139579197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The purpose of this study was to develop a UPLC-MS/MS method for the determination of icotinib concentrations in blood plasma. Method: For plasma sample preparation, protein precipitation with acetonitrile was utilized. Analytes were separated on a Kinetex C18 column using 10 mM ammonium acetate containing 0.2% formic acid and methanol (30:70) as the mobile phase, with a gradient flow rate ranging from 0.2 ml·min-1 to 0.4 ml·min-1. The total chromatographic analysis duration was 4.5 minutes. The UPLC system was connected to a mass spectrometer via an electrospray ionization (ESI) interface operated in positive ion mode. Mass monitoring was conducted in multiple reaction monitoring (MRM) modes, with precursor-to-product transitions being m/z 392.06→304.07 for icotinib and m/z 248.00→120.09 for the internal standard, tinidazole. This method has been used for a pharmacokinetic study in rats that were orally administered a single dose of 30 mg/kg icotinib. Result: The assay showed good linearity over concentration ranges of 1-1000 ng/ml for icotinib, with the correlation coefficient exceeding 0.99. The lower limit of quantitation (LLOQ) was established at 1 ng/ml. Both intra- and inter-day precisions (RSD, %) were below 8.23%. The results demonstrated that stability, matrix effect, extraction recovery, carryover effect and dilution stability were all within the acceptable conditions. The primary pharmacokinetic parameters in SD rats after oral administration of icotinib (30 mg·kg-1 ) were as follows: t1/2 = (2.92 ± 0.87)h, Cmax = (2168.65 ± 268.72)ng/ml, Tmax = (0.70 ± 0.27)h, AUC=(9.69 ± 1.95)ug/mL•h, Vd = (14.51 ± 5.60)L, and CL = (3.19 ± 0.59)L/h. Conclusion: A simple and sensitive UPLC-MS/MS method was developed and validated for the determination of icotinib in pharmacokinetic studies.
{"title":"Determination of Tyrosine Kinase Inhibitor Icotinib in Rat Plasma Using UPLC-MS/MS and its Application in In Vivo Pharmacokinetic","authors":"Xuewei Zhao, Ruoyang Li, Zhangying Feng, Shanshan Chen, Yu Liang, Jinglin Gao, Mingxia Wang","doi":"10.2174/0115734129276657231130055912","DOIUrl":"https://doi.org/10.2174/0115734129276657231130055912","url":null,"abstract":"Objective: The purpose of this study was to develop a UPLC-MS/MS method for the determination of icotinib concentrations in blood plasma. Method: For plasma sample preparation, protein precipitation with acetonitrile was utilized. Analytes were separated on a Kinetex C18 column using 10 mM ammonium acetate containing 0.2% formic acid and methanol (30:70) as the mobile phase, with a gradient flow rate ranging from 0.2 ml·min-1 to 0.4 ml·min-1. The total chromatographic analysis duration was 4.5 minutes. The UPLC system was connected to a mass spectrometer via an electrospray ionization (ESI) interface operated in positive ion mode. Mass monitoring was conducted in multiple reaction monitoring (MRM) modes, with precursor-to-product transitions being m/z 392.06→304.07 for icotinib and m/z 248.00→120.09 for the internal standard, tinidazole. This method has been used for a pharmacokinetic study in rats that were orally administered a single dose of 30 mg/kg icotinib. Result: The assay showed good linearity over concentration ranges of 1-1000 ng/ml for icotinib, with the correlation coefficient exceeding 0.99. The lower limit of quantitation (LLOQ) was established at 1 ng/ml. Both intra- and inter-day precisions (RSD, %) were below 8.23%. The results demonstrated that stability, matrix effect, extraction recovery, carryover effect and dilution stability were all within the acceptable conditions. The primary pharmacokinetic parameters in SD rats after oral administration of icotinib (30 mg·kg-1 ) were as follows: t1/2 = (2.92 ± 0.87)h, Cmax = (2168.65 ± 268.72)ng/ml, Tmax = (0.70 ± 0.27)h, AUC=(9.69 ± 1.95)ug/mL•h, Vd = (14.51 ± 5.60)L, and CL = (3.19 ± 0.59)L/h. Conclusion: A simple and sensitive UPLC-MS/MS method was developed and validated for the determination of icotinib in pharmacokinetic studies.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"147 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139579284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background:: Previous studies of dextromethorphan hydrobromide basically worked on simultaneous research with other compounds. So, the development of a novel method using the isocratic elution mode is needed. Objective:: For the detection of dextromethorphan hydrobromide (DXM) in diverse matrices, a straightforward, accurate, and sensitive reversed-phase HPLC technique using a Waters 2487 Dual λ Absorbance detector has been designed and validated. Method:: In this experimental work, utilizing methanol/pH 3.0 potassium dihydrogen phosphate buffer (70:30, v/v) as the mobile phase, the separation was completed in 7 minutes on a C-18 HPLC column (4.6 cm length, 4.6 mm internal diameter; 5 μm particle size) utilizing an isocratic elution mode, flow rate of 1.0 mL/min, and UV-detection at 278 nm. Integration of the chromatography response was carried out using Empower 2.4 software Results:: With an R2 of 0.9987, the current approach showed high linearity for DXM in the 10- 60 ppm range (retention time 4.281 ± 0.505 min). For DXM Hbr, the limits of detection (LOD & LOQ) were 10.633 μg/mL and 32.221μg/mL, respectively. Samples remained stable in the presence of the matrices without any apparent influence. Conclusion:: The novel approach, which used a straightforward liquid/liquid extraction procedure with recovery ranging from 100 ± 10 % performed by two different analytes, was accurate. The precision within and between days was ≤ 2.0% (RSD). The technique was proven to be reliable and repeatable, and it can be utilized with pharmacological (active ingredients, syrups) and also for biological (blood) matrices which can be used in future research work for bioanalytical method development such as pharmacokinetics studies.
{"title":"Isocratic RP-HPLC Method Development, Validation, and Optimization of BCS-II in Bulk and Dosage Form","authors":"Uditi Handa, Anuj Malik, Kumar Guarve, Fatimah Jan, Kajal Nagpal","doi":"10.2174/0115734129283491240103071614","DOIUrl":"https://doi.org/10.2174/0115734129283491240103071614","url":null,"abstract":"Background:: Previous studies of dextromethorphan hydrobromide basically worked on simultaneous research with other compounds. So, the development of a novel method using the isocratic elution mode is needed. Objective:: For the detection of dextromethorphan hydrobromide (DXM) in diverse matrices, a straightforward, accurate, and sensitive reversed-phase HPLC technique using a Waters 2487 Dual λ Absorbance detector has been designed and validated. Method:: In this experimental work, utilizing methanol/pH 3.0 potassium dihydrogen phosphate buffer (70:30, v/v) as the mobile phase, the separation was completed in 7 minutes on a C-18 HPLC column (4.6 cm length, 4.6 mm internal diameter; 5 μm particle size) utilizing an isocratic elution mode, flow rate of 1.0 mL/min, and UV-detection at 278 nm. Integration of the chromatography response was carried out using Empower 2.4 software Results:: With an R2 of 0.9987, the current approach showed high linearity for DXM in the 10- 60 ppm range (retention time 4.281 ± 0.505 min). For DXM Hbr, the limits of detection (LOD & LOQ) were 10.633 μg/mL and 32.221μg/mL, respectively. Samples remained stable in the presence of the matrices without any apparent influence. Conclusion:: The novel approach, which used a straightforward liquid/liquid extraction procedure with recovery ranging from 100 ± 10 % performed by two different analytes, was accurate. The precision within and between days was ≤ 2.0% (RSD). The technique was proven to be reliable and repeatable, and it can be utilized with pharmacological (active ingredients, syrups) and also for biological (blood) matrices which can be used in future research work for bioanalytical method development such as pharmacokinetics studies.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"7 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139579336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-09DOI: 10.2174/0115734129247763231224172204
Lucas Prosperi Ferreira, Marcus Vinicius Martins Rubatino, Magali Benjamim de Araújo, Rudy Bonfilio
Background:: Highly purified water is essential for the production of pharmaceuticals, directly impacting the quality and safety of the final product. Method:: In this work, we studied the physicochemical and microbiological quality of 1477 purified water samples from 25 compounding pharmacies in Southeast Brazil. To the best of our knowledge, this is the most comprehensive study on the quality of water purified in Brazil. It was observed that 47.7% of the samples were purified by reverse osmosis, 39.9% by distillation and 12.4% by deionization. Of the total, 10.63% presented one or more non-compliances. Amongst the three purification processes, the amount of non-compliance was found to be 8.9% for reverse osmosis, 10.9% for deionization, and 12.4% for distillation. Result:: It was therefore concluded that reverse osmosis is advantageous. However, even the advantageous reverse osmosis process showed contamination by viable bacteria, total and faecal coliforms/ E. coli, and Pseudomonas aeruginosa. Conclusion:: Quantitative data showed that all purification processes significantly reduced the conductivity and pH values of the input water. However, conductivity values above the limits and several other non-compliances were found after purification by all processes, which points to the need for additional studies on improvements in purification processes adopted by compounding pharmacies in Brazil.
{"title":"Evaluation of the Quality of Water Samples Purified by Compounding Pharmacies in Brazil","authors":"Lucas Prosperi Ferreira, Marcus Vinicius Martins Rubatino, Magali Benjamim de Araújo, Rudy Bonfilio","doi":"10.2174/0115734129247763231224172204","DOIUrl":"https://doi.org/10.2174/0115734129247763231224172204","url":null,"abstract":"Background:: Highly purified water is essential for the production of pharmaceuticals, directly impacting the quality and safety of the final product. Method:: In this work, we studied the physicochemical and microbiological quality of 1477 purified water samples from 25 compounding pharmacies in Southeast Brazil. To the best of our knowledge, this is the most comprehensive study on the quality of water purified in Brazil. It was observed that 47.7% of the samples were purified by reverse osmosis, 39.9% by distillation and 12.4% by deionization. Of the total, 10.63% presented one or more non-compliances. Amongst the three purification processes, the amount of non-compliance was found to be 8.9% for reverse osmosis, 10.9% for deionization, and 12.4% for distillation. Result:: It was therefore concluded that reverse osmosis is advantageous. However, even the advantageous reverse osmosis process showed contamination by viable bacteria, total and faecal coliforms/ E. coli, and Pseudomonas aeruginosa. Conclusion:: Quantitative data showed that all purification processes significantly reduced the conductivity and pH values of the input water. However, conductivity values above the limits and several other non-compliances were found after purification by all processes, which points to the need for additional studies on improvements in purification processes adopted by compounding pharmacies in Brazil.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"128 22 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139411417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.2174/0115734129281427231123063958
Li Fu, Jiangwei Zhu, Qingwei Zhou
: Veterinary drug residues in foods pose risks to consumers and promote antimicrobial resistance. Effective detection methods are needed to monitor and control residues. Recent advancements in analytical techniques for veterinary drug residue detection were reviewed. Key sample preparation methods, including QuEChERS, SPE, ASE, and LLE, were summarized. Instrumental analysis techniques including LC-MS/MS, GC-MS, immunoassays, CE and biosensors were examined. Recent trends and future directions were identified. LC-MS/MS and GC-MS provide the highest sensitivity and specificity for veterinary drug residue analysis. However, selectivity remains a challenge, particularly for complex matrices like meat and liver. Multi-residue methods now cover over 100 analytes, but analyzing new and legacy drugs lacking established methods is difficult. Increased sensitivity has been achieved through UHPLC and high resolution MS, but detection limits below 1 μg/kg often remain elusive. sSimplified on-site tests are gaining interest. More selective extraction strategies, data-driven multi-residue methods, microflow LC, and integrated analytical platforms may help address current challenges. Continued advances in sample preparation, instrumentation, data processing, and validation will be needed to fully realize the potential of veterinary drug residue detection and ensure food safety.
{"title":"Improved Detection of Veterinary Drug Residues: Advancing Analytical Techniques to Ensure Food Safety","authors":"Li Fu, Jiangwei Zhu, Qingwei Zhou","doi":"10.2174/0115734129281427231123063958","DOIUrl":"https://doi.org/10.2174/0115734129281427231123063958","url":null,"abstract":": Veterinary drug residues in foods pose risks to consumers and promote antimicrobial resistance. Effective detection methods are needed to monitor and control residues. Recent advancements in analytical techniques for veterinary drug residue detection were reviewed. Key sample preparation methods, including QuEChERS, SPE, ASE, and LLE, were summarized. Instrumental analysis techniques including LC-MS/MS, GC-MS, immunoassays, CE and biosensors were examined. Recent trends and future directions were identified. LC-MS/MS and GC-MS provide the highest sensitivity and specificity for veterinary drug residue analysis. However, selectivity remains a challenge, particularly for complex matrices like meat and liver. Multi-residue methods now cover over 100 analytes, but analyzing new and legacy drugs lacking established methods is difficult. Increased sensitivity has been achieved through UHPLC and high resolution MS, but detection limits below 1 μg/kg often remain elusive. sSimplified on-site tests are gaining interest. More selective extraction strategies, data-driven multi-residue methods, microflow LC, and integrated analytical platforms may help address current challenges. Continued advances in sample preparation, instrumentation, data processing, and validation will be needed to fully realize the potential of veterinary drug residue detection and ensure food safety.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"31 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138691921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.2174/0115734129254806231127110951
Avani Gupta, Juber Akhtar, Kailash Chandra Rastogi, Badruddeen, Mohammad Irfan Khan, Mohammad Ahmad
Background: A high-performance liquid chromatography (HPLC) method was developed for the determination of Pantoprazole Sodium (PPZ) in the presence of its degradation products. The degradation of PPZ was studied in simulated intestinal fluid (SIF) and simulated gastric fluids (SGF) in various temperature conditions. Aim: This study aimed to establish a simple, sensitive, and rapid RP HPLC method for in-vitro determination of Pantoprazole Sodium and its degradation products in simulated gastric and intestinal fluids. Objective: Pantoprazole is acid labile drug. In order to determine pantoprazole in various oral dosage forms, the stability-indicating assay of PPZ was performed in phosphate buffer (pH 6.8) representing simulated intestinal fluid (SIF) and in 0.1 molars (M) Hydrochloric acid (HCl) as simulated gastric fluid (SGF) at two different temperature conditions, i.e., 25°C and 0°C, respectively. Method: Pantoprazole sodium was obtained from the Akums laboratory in Haridwar. The analysis was performed by high-performance liquid chromatography (HPLC), Shimadzu, equipped with two LC-10 AD VP solvent-delivery modules, a SPD-10A UV–-visible detector, and a manual injector valve with 20 μL sample loop. Phenomenex ODS analytical column (150 mm × 4.6 mm i.d., 5 μm particles) was done under reversed-phase partition chromatographic conditions. The mobile phase was phosphate buffer and acetonitrile (ACN) of pH 7.4, respectively, optimized in a 70:30 (v/v) ratio followed by filtration through a 0.45 μm membrane filter and degassed by ultrasonicator before use. The mobile phase was delivered at the flow rate of 2 mL/min. The various parameters, such as linearity, accuracy and precision of the analytical method, were studied. Result: The standard curve of PPZ was linear (R2>0.99) over the concentration range of 5-30 μg/mL, and the relative standard deviation (RSD) values for intra-day and inter-day variations were in the range of 1.0-1.8%. The range of RSD was within ±2. Conclusion: The stability of PPZ in aqueous solution was pH dependent. The rate of degradation increases with decreasing pH. The pH stability of pantoprazole was studied at the above-mentioned temperature conditions. The PPZ peaks were analyzed by comparing them with fresh samples and were stable in SIF solution after 24 hours elapsed time at pH 6.8. The obtained degraded peaks in SGF (pH 1) were successfully separated from the PPZ.
{"title":"Stability Indicating HPLC Method for In-Vitro Determination of Pantoprazole Sodium and its Degradation Products in Simulated Gastric and Intestinal Fluids","authors":"Avani Gupta, Juber Akhtar, Kailash Chandra Rastogi, Badruddeen, Mohammad Irfan Khan, Mohammad Ahmad","doi":"10.2174/0115734129254806231127110951","DOIUrl":"https://doi.org/10.2174/0115734129254806231127110951","url":null,"abstract":"Background: A high-performance liquid chromatography (HPLC) method was developed for the determination of Pantoprazole Sodium (PPZ) in the presence of its degradation products. The degradation of PPZ was studied in simulated intestinal fluid (SIF) and simulated gastric fluids (SGF) in various temperature conditions. Aim: This study aimed to establish a simple, sensitive, and rapid RP HPLC method for in-vitro determination of Pantoprazole Sodium and its degradation products in simulated gastric and intestinal fluids. Objective: Pantoprazole is acid labile drug. In order to determine pantoprazole in various oral dosage forms, the stability-indicating assay of PPZ was performed in phosphate buffer (pH 6.8) representing simulated intestinal fluid (SIF) and in 0.1 molars (M) Hydrochloric acid (HCl) as simulated gastric fluid (SGF) at two different temperature conditions, i.e., 25°C and 0°C, respectively. Method: Pantoprazole sodium was obtained from the Akums laboratory in Haridwar. The analysis was performed by high-performance liquid chromatography (HPLC), Shimadzu, equipped with two LC-10 AD VP solvent-delivery modules, a SPD-10A UV–-visible detector, and a manual injector valve with 20 μL sample loop. Phenomenex ODS analytical column (150 mm × 4.6 mm i.d., 5 μm particles) was done under reversed-phase partition chromatographic conditions. The mobile phase was phosphate buffer and acetonitrile (ACN) of pH 7.4, respectively, optimized in a 70:30 (v/v) ratio followed by filtration through a 0.45 μm membrane filter and degassed by ultrasonicator before use. The mobile phase was delivered at the flow rate of 2 mL/min. The various parameters, such as linearity, accuracy and precision of the analytical method, were studied. Result: The standard curve of PPZ was linear (R2>0.99) over the concentration range of 5-30 μg/mL, and the relative standard deviation (RSD) values for intra-day and inter-day variations were in the range of 1.0-1.8%. The range of RSD was within ±2. Conclusion: The stability of PPZ in aqueous solution was pH dependent. The rate of degradation increases with decreasing pH. The pH stability of pantoprazole was studied at the above-mentioned temperature conditions. The PPZ peaks were analyzed by comparing them with fresh samples and were stable in SIF solution after 24 hours elapsed time at pH 6.8. The obtained degraded peaks in SGF (pH 1) were successfully separated from the PPZ.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"42 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background:: The liver perfusion method is frequently used in drug pharmacokinetic studies and the various effects of drugs on liver tissue. The aim of this study was to establish and validate an analytical method using high-performance liquid chromatography to determine the simultaneous concentration of losartan and its active metabolite, EXP-3174, in an isolated perfused rat liver study. Method:: An HPLC system with isocratic mode was used. Various chromatographic parameters were adjusted to develop and validate a method for determination of losartan and its active metabolite in liver perfusion media. Results:: In this study, losartan and its active metabolite, EXP-3174, were separated using a C18 stationary phase, a mobile phase consisting of acetonitrile: phosphate buffer at a flow rate of 1 mL.min-1, and UV detection at 254 nm. Retention times for losartan and the metabolite were 10 and 16 minutes, respectively. Linearity from 25-250 ng.ml-1 was validated with acceptable accuracy and precision. The LOD and LOQ for losartan were 7.0 and 21.1 ng.ml-1, respectively. The LOD and LOQ for metabolite were 7.4 and 22.4 ng.ml-1, respectively. ChromGate® software was used to acquire and process the data. Conclusions:: The optimized and validated technique was effectively used to analyze losartan and its active metabolite in isolated perfused rat liver.
{"title":"Development and Validation of an Analytical RP-HPLC Method for Simultaneous Estimation of Losartan and its Active Metabolite (EXP-3174) in Isolated Perfused Rat Liver","authors":"Mahsa Toolabi, Reyhaneh Ramezankhani, Nadereh Rahbar, Maryam Dibaei, Alireza foroumadi, Hoda Lavasani, Vida Kazemi, Mohammadreza Rouini","doi":"10.2174/0115734129272952231103080114","DOIUrl":"https://doi.org/10.2174/0115734129272952231103080114","url":null,"abstract":"Background:: The liver perfusion method is frequently used in drug pharmacokinetic studies and the various effects of drugs on liver tissue. The aim of this study was to establish and validate an analytical method using high-performance liquid chromatography to determine the simultaneous concentration of losartan and its active metabolite, EXP-3174, in an isolated perfused rat liver study. Method:: An HPLC system with isocratic mode was used. Various chromatographic parameters were adjusted to develop and validate a method for determination of losartan and its active metabolite in liver perfusion media. Results:: In this study, losartan and its active metabolite, EXP-3174, were separated using a C18 stationary phase, a mobile phase consisting of acetonitrile: phosphate buffer at a flow rate of 1 mL.min-1, and UV detection at 254 nm. Retention times for losartan and the metabolite were 10 and 16 minutes, respectively. Linearity from 25-250 ng.ml-1 was validated with acceptable accuracy and precision. The LOD and LOQ for losartan were 7.0 and 21.1 ng.ml-1, respectively. The LOD and LOQ for metabolite were 7.4 and 22.4 ng.ml-1, respectively. ChromGate® software was used to acquire and process the data. Conclusions:: The optimized and validated technique was effectively used to analyze losartan and its active metabolite in isolated perfused rat liver.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138552471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-04DOI: 10.2174/0115734129270782231123103912
Ji-Hye Shin, Joo-Eun Kim
Background: Recently, a combination prescription with the main ingredients sitagliptin and dapagliflozin as dipeptidyl peptidase-4 andsodium–glucose cotransporter-2 inhibitors, respectively, for the treatment of type 2 diabetes has widely been issued in hospitals. However, the development of double-layered tablets requires simultaneous quantitative dissolution tests that are significantly efficient and cost-effective. Objective: Individual analysis of the two active pharmaceutical ingredients (APIs) incurs more than twice the time and cost. Consequently, this study aimed to develop a dissolution analysis method that simultaneously quantifies the APIs dapagliflozin and sitagliptin in multilayered tablets. This simultaneous quantitative dissolution analysis can dramatically reduce analysis time and cost. Methods: For reversed-phase high-performance liquid chromatography (RP-HPLC) analysis using ultraviolet detection, a Zorbax C18 column (4.6 × 150 mm, 5 μm) was used, and the flow rate was 1.5 mL/min, injection amount 20 μL, and maximum absorption wavelength set to 205 nm. Additionally, the analysis time was set to 1.5 times the retention time of dapagliflozin Results: The retention times of dapagliflozin and sitagliptin were 11.57 and 2.56 min, respectively. Further, their relative standard deviations were 0.11% and 0.05%, respectively. Quantitative analysis using RP-HPLC confirmed no peak interference between the APIs and excipients. Both APIs exhibited linearity at a 20–120% concentration. Conclusion: The dissolution method developed in this study can quantify both APIs simultaneously, thereby reducing analysis time and cost by more than 50% and increasing efficiency in the pharmaceutical industry.
{"title":"Development and Validation of Simultaneous Quantitative Dissolution Analysis for the Two Active Pharmaceutical Ingredients in Dapagliflozin Propanediol Monohydrate–Sitagliptin Phosphate Monohydrate Multi-Layered Tablets","authors":"Ji-Hye Shin, Joo-Eun Kim","doi":"10.2174/0115734129270782231123103912","DOIUrl":"https://doi.org/10.2174/0115734129270782231123103912","url":null,"abstract":"Background: Recently, a combination prescription with the main ingredients sitagliptin and dapagliflozin as dipeptidyl peptidase-4 andsodium–glucose cotransporter-2 inhibitors, respectively, for the treatment of type 2 diabetes has widely been issued in hospitals. However, the development of double-layered tablets requires simultaneous quantitative dissolution tests that are significantly efficient and cost-effective. Objective: Individual analysis of the two active pharmaceutical ingredients (APIs) incurs more than twice the time and cost. Consequently, this study aimed to develop a dissolution analysis method that simultaneously quantifies the APIs dapagliflozin and sitagliptin in multilayered tablets. This simultaneous quantitative dissolution analysis can dramatically reduce analysis time and cost. Methods: For reversed-phase high-performance liquid chromatography (RP-HPLC) analysis using ultraviolet detection, a Zorbax C18 column (4.6 × 150 mm, 5 μm) was used, and the flow rate was 1.5 mL/min, injection amount 20 μL, and maximum absorption wavelength set to 205 nm. Additionally, the analysis time was set to 1.5 times the retention time of dapagliflozin Results: The retention times of dapagliflozin and sitagliptin were 11.57 and 2.56 min, respectively. Further, their relative standard deviations were 0.11% and 0.05%, respectively. Quantitative analysis using RP-HPLC confirmed no peak interference between the APIs and excipients. Both APIs exhibited linearity at a 20–120% concentration. Conclusion: The dissolution method developed in this study can quantify both APIs simultaneously, thereby reducing analysis time and cost by more than 50% and increasing efficiency in the pharmaceutical industry.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"44 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138512671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.2174/0115734129246067230921050607
Gregory K. Webster
Aims: The aim of this project was to develop a QC friendly and efficient method of protein species of origin identification to replace more costly mass spectrometric based methods currently being used for this testing. Background: NMR relaxation measurements with proteins in aqueous solutions exploit the fast chemical exchange between water and exposed NH and OH protons of amino acid side chains in the folded protein structure unique to each biologic drug. Implementation of this technique has led to routine testing for authentication and forensics of biopharmaceuticals, determination of moisture content in lyophilized protein formulations and aggregation of proteins in solution. For small molecule applications, TD-NMR can detect if solvents are received neat or tainted with moisture, impurities, or denaturants. Objective: The objective of this study was to evaluate the ability of NMR Relaxation measurements to differentiate between sources of Albumin proteins as a rapid QC test. Evaluation of differences in molecular mobility between components in a solution as reflected in the longitudinal (T1) and transverse (T2) relaxation times of protons demonstrate that NMR relaxation techniques can distinguish between different albumin sources of origin. Methods: Representative albumin proteins from differing sources of origin were studied. Using bovine serum albumin (BSA) as the target species of origin, NMR relaxation techniques as well as chemometric modeling were used to evaluate the use of this technique for protein source of origin identification. Results: NMR Relaxation using benchtop instrumentation showed that the bovine albumin species of origin can be distinguished from porcine, chicken egg white and sheep sources of origin. Goat albumin selectivity remained questionable and BSA cannot be distinguished from human or rabbit sources of origin within the representative variability. T2 transverse relaxation results were significantly more discriminating for protein source identification than the T1 longitudinal relaxation result by itself. The T1 longitudinal relaxation result did not contribute significantly to this investigation. However, fusing the T1 data with the T2 transverse relaxation results and using larger data sets merit further evaluation in the hope of achieving additional selectivity. Conclusion: While additional lots are needed for more definitive results, this preliminary evaluation of using NMR Relaxation demonstrated the capability for the source of origin species discrimination and identification using benchtop NMR instrumentation.
{"title":"Protein Species of Origin Determination By NMR Relaxometry","authors":"Gregory K. Webster","doi":"10.2174/0115734129246067230921050607","DOIUrl":"https://doi.org/10.2174/0115734129246067230921050607","url":null,"abstract":"Aims: The aim of this project was to develop a QC friendly and efficient method of protein species of origin identification to replace more costly mass spectrometric based methods currently being used for this testing. Background: NMR relaxation measurements with proteins in aqueous solutions exploit the fast chemical exchange between water and exposed NH and OH protons of amino acid side chains in the folded protein structure unique to each biologic drug. Implementation of this technique has led to routine testing for authentication and forensics of biopharmaceuticals, determination of moisture content in lyophilized protein formulations and aggregation of proteins in solution. For small molecule applications, TD-NMR can detect if solvents are received neat or tainted with moisture, impurities, or denaturants. Objective: The objective of this study was to evaluate the ability of NMR Relaxation measurements to differentiate between sources of Albumin proteins as a rapid QC test. Evaluation of differences in molecular mobility between components in a solution as reflected in the longitudinal (T1) and transverse (T2) relaxation times of protons demonstrate that NMR relaxation techniques can distinguish between different albumin sources of origin. Methods: Representative albumin proteins from differing sources of origin were studied. Using bovine serum albumin (BSA) as the target species of origin, NMR relaxation techniques as well as chemometric modeling were used to evaluate the use of this technique for protein source of origin identification. Results: NMR Relaxation using benchtop instrumentation showed that the bovine albumin species of origin can be distinguished from porcine, chicken egg white and sheep sources of origin. Goat albumin selectivity remained questionable and BSA cannot be distinguished from human or rabbit sources of origin within the representative variability. T2 transverse relaxation results were significantly more discriminating for protein source identification than the T1 longitudinal relaxation result by itself. The T1 longitudinal relaxation result did not contribute significantly to this investigation. However, fusing the T1 data with the T2 transverse relaxation results and using larger data sets merit further evaluation in the hope of achieving additional selectivity. Conclusion: While additional lots are needed for more definitive results, this preliminary evaluation of using NMR Relaxation demonstrated the capability for the source of origin species discrimination and identification using benchtop NMR instrumentation.","PeriodicalId":10889,"journal":{"name":"Current Pharmaceutical Analysis","volume":"45 6","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138512669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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