ABSTRACT
An efficient one-pot three-component reaction for the synthesis of [1,3]dioxolo[4',5':6,7]chromeno[2,3-b]pyridines 4(a-i) has been developed. Synthesis was achieved by reacting sesamol (1), aromatic aldehydes 2(a-i), and 2-aminopropene-1,1,3-tricarbonitrile (3) in the presence of triethylamine at 100 °C under neat reaction condition. Simple operational procedure, broad substrate scope, column chromatography free separations, and high yield of products make it an efficient and largely acceptable synthetic strategy. Synthesized compounds 4(a-i) were further screened for preliminary anticonvulsant activity using MES and scPTZ tests. These analogs were also checked for neurotoxicity and hepatotoxicity. Selected active compounds have been then screened quantitatively to determine ED50 and TD50 values. Analog 4h was found effective in both preclinical seizure models with significant therapeutic/toxicity profile (4h: ED50 = 34.7 mg/kg, MES test; ED50 = 37.9 mg/kg, scPTZ test; TD50 = 308.7 mg/kg). Molecular dynamic simulation for 100 ns of compound 4h-complexed with GABAA receptor revealed good thermodynamic behavior and fairly stable interactions (4h, Docking score = - 10.94). In conclusion, effective synthetic strategy, significant anticonvulsant activity with good toxicity profile and detailed molecular modeling studies led us to anticipate the emergence of these analogs as valid leads for the development of future effective neurotherapeutic agents.
Subject(s)
Anticonvulsants , Pyridines , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Anticonvulsants/chemistry , Structure-Activity Relationship , Pyridines/pharmacology , Pyridines/therapeutic use , Receptors, GABA-A , Molecular Dynamics Simulation , Drug Design , Molecular StructureABSTRACT
Ambroxol (AMB) is a member of the expectorant class, widely used as a secreolytic agent in patients to break up secretions. AMB is rapidly and effectively distributed from blood to tissue. The lungs have the highest concentration of AMB; accumulation of AMB in human lung tissue was detected at concentrations 15- to 20-fold greater than those reported in the circulation. Because of its wide range of actions and therapeutic applications may be worth looking into, particularly for respiratory symptoms, antioxidant, anti-inflammatory, influenza, and rhinovirus infections. Though several analytical methodologies have been established and confirmed for the AMB analysis in matrices of pharmaceutical and biological origins, novel sustainable, and economical methods are still to be choice of protocol to increase its sensitivity, reliability, and repeatability. Therefore, the present review offers an overview of critical analytical aspects regarding the HPLC, LC-MS/MS, HPTLC, capillary electrophoresis, spectrophotometry, and electrochemical methods for quantifying AMB in pharmaceutical and biological samples. Furthermore, this review will thoroughly discuss the physicochemical properties, stability, extraction conditions, instrumentation, and operational parameters of the targeted analyte. As a result, for the first time, this review complies with vital background information and an up-to-date interpretation of research undertaken by anticipated methodologies examined and implemented for the pharmaceutical analysis AMB.
Subject(s)
Ambroxol , Ambroxol/therapeutic use , Anti-Inflammatory Agents , Antioxidants , Chromatography, Liquid , Expectorants/therapeutic use , Humans , Pharmaceutical Preparations , Reproducibility of Results , Tandem Mass SpectrometryABSTRACT
Three crucial anticancer scaffolds, namely indolin-2-one, 1,3,4-thiadiazole, and aziridine, are explored to synthesize virtually screened target molecules based on the c-KIT kinase protein. The stem cell factor receptor c-KIT was selected as target because most U.S. FDA-approved receptor tyrosine kinase inhibitors bearing the indolin-2-one scaffold profoundly inhibit c-KIT. Molecular hybrids of indolin-2-one with 1,3,4-thiadiazole (IIIa-m) and aziridine (VIa and VIc) were afforded through a modified Schiff base green synthesis using ß-cyclodextrin-SO3H in water as a recyclable proton-donor catalyst. A computational study found that indolin-2,3-dione forms a supramolecular inclusion complex with ß-cyclodextrin-SO3H through noncovalent interactions. A molecular docking study of all the synthesized compounds was executed on the c-KIT kinase domain, and most compounds displayed binding affinities similar to that of Sunitinib. On the basis of the pharmacokinetic significance of the aryl thioether linkage in small molecules, 1,3,4-thiadiazole hybrids (IIIa-m) were extended to a new series of 3-((5-(phenylthio)-1,3,4-thiadiazol-2-yl)imino)indolin-2-ones (IVa-m) via thioetherification using bis(triphenylphosphine)palladium(II)dichloride as the catalyst for C-S bond formation. Target compounds were tested against NCI-60 human cancer cell lines for a single-dose concentration. Among all three series of indolin-2-ones, the majority of compounds demonstrated broad-spectrum activity toward various cancer cell lines. Compounds IVc and VIc were further evaluated for a five-dose anticancer study. Compound IVc showed a potent activity of IC50 = 1.47 µM against a panel of breast cancer cell lines, whereas compound VIc exhibited the highest inhibition for a panel of colon cancer cell lines at IC50 = 1.40 µM. In silico ADME property descriptors of all the target molecules are in an acceptable range. Machine learning algorithms were used to examine the metabolites and phase I and II regioselectivities of compounds IVc and VIc, and the results suggested that these two compounds could be potential leads for the treatment of cancer.
ABSTRACT
Rufinamide is used presently to treat Lenaux-Gastaut syndrome. A full factorial design and desirability approach was investigated for the optimization of hydrolytic stress via response surface curves (RSCs). The degradation impurities were identified and resolved using reversed-phase high-performance liquid chromatography (RP-HPLC) on the Qualisil® BDS C8 column. Acetonitrile-water (29:71, v/v) was optimized for the mobile phase and used at a flow rate of 1.0 ml/min with detection at a wavelength of 230 nm. Rufinamide showed appreciable susceptibility to hydrolysis under acidic and alkaline stress, and substantial degradation in the neutral condition. It degraded much less under oxidative stress. Exposure towards thermal and photolytic stress conditions indicated appreciable stability. The developed method was subjected to validation as per the recommendations of the International Conference on Harmonization. The proposed method showed no influence from the excipients and the degradation products. As well as good precision and accuracy in determination, the method showed a linear response between 2 and 12 µg ml-1 . The method was extended for determination in a human plasma sample, which resulted in excellent recovery without interference from matrix effects. The combined use of desirability and design for the optimization of acidic and alkaline hydrolytic stress led to simple and rapid analysis.
Subject(s)
Chromatography, Reverse-Phase , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Drug Stability , Humans , Reproducibility of Results , TriazolesABSTRACT
Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is prescribed in the form of racemic mixture and S- form is a more influential isomer. Acenocoumarol starts quickly with action and absorption, and the effect lasts for 15-20 h. In most patients, the therapeutic prothrombin range is caused 36 h after the primary dose. This review offers a detailed overview of the various analytical methodologies published in the literature from 1976 to uptil now for evaluation acenocoumarol and its combinations in specimens. The present review also stated the chiral analytical methods for the quantification of its enantiomers. A detailed study of the work revealed several analytical methodologies are routinely used for estimation of acenocoumarol includes UV/Vis-Spectrophotometry, liquid chromatography-mass spectrophotometry, high-performance liquid-chromatography, gas chromatography, high-performance thin-layer chromatography, capillary electrophoresis, Fourier-transform infrared spectroscopy and many miscellaneous techniques. Pharmaceutical analysis carried out the prominent task to understand the knowledge of the physicochemical properties of the medicinal agent; since the establishment of a new analytical method is still a challenging task for a research scientist. Thus, the present review will help to research scientist for the development of new analytical methods for the acenocoumarol.
Subject(s)
Acenocoumarol , Electrophoresis, Capillary , Chromatography, High Pressure Liquid/methods , Chromatography, Thin Layer , Humans , Pharmaceutical PreparationsABSTRACT
An experimental combination of analytical quality by design and green analytical chemistry approaches is introduced to develop an high-performance thin-layer chromatography (HPTLC) approach to quantify barnidipine hydrochloride in the pharmaceutical matrix. The analytical quality by design approach was introduced to green analytical chemistry to enhance protocol knowledge while ensuring efficiency and reducing environmental impacts, energy consumption and analyst visibility. This analytical approach was systematically addressed by exploring failure mode effect analysis, risk assessment and optimization design. Subsequently, a screening of primary variables was performed to select the aptest proportion of solvents in the mobile phase resulting from the principles of green analytical chemistry. Failure mode effect analysis and a risk assessment study were attempted to estimate the critical method parameters (CMPs). The influence of the CMPs on critical analytical attributes, i.e. retention factor and peak area, was assessed through a screening design. A response surface methodology was then executed for the critical analytical attributes as a concern of the determined CMPs, and the conditions for excellent resolution were determined using a desirability procedure. The established protocol was validated in compliance with the International Conference on Harmonization guideline Q2(R1) and showed excellent specificity and sensitivity.
Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, Thin Layer/methods , Green Chemistry Technology/methods , Nifedipine/analogs & derivatives , Limit of Detection , Linear Models , Nifedipine/analysis , Reproducibility of Results , Research DesignABSTRACT
Terahertz (THz) spectroscopy is an emerging field for quality control of pharmaceuticals, which uses T-waves for detection. T-waves fall in between infrared and microwave radiations while possessing some of the characteristics of both. THz spectroscopy reveals its existence in between 0.1 and 10 THz. These radiations have the ability to penetrate a broad range of non-conductive materials and it is nonionizing. The first article stating the use of THz radiations was found in late 1960 for the generation of the astronomical images. This review essentially creates attention toward different forms and instrumentation of THz spectroscopy along with the updates for timely and upbeat pharmaceutical applications. The most frequently used technique is THz-TDS which has profoundly privileged applicability for the pharmaceuticals. The existing literature of THz spectroscopy further created albeit interest to explore the applications for future implementation in concern with the pharmaceuticals. The review critically outlines here all the pharmaceutical applications of THz spectroscopy including protein analyses, crystallinity studies, evaluating tablet films and coats, medicinal aging variations, and detection of illicit drugs, along with the advantages over traditional techniques. The other side of THz spectroscopy stating limitations is also studied and taken into the note to present here. This review is a genuine attempt to quote and crucially assess the possible as well as anticipated prospectives for the pharmaceuticals. The present article will further promote the awareness, opportunities, and scientific exploration of this exciting technology as THz spectroscopy.
Subject(s)
Pharmaceutical Preparations , Terahertz Spectroscopy , Prospective Studies , Quality Control , Terahertz Spectroscopy/methodsABSTRACT
The hydrotropy though existing as precisely used scientific approach assisting solubilization for all. It took 66 long years to use the concept in drug analysis since its inception in 1916 and first use for facilitation of drug solubility toward better pharmaceutical analysis in 1982. Considering the unending importance in pharmaceutical sciences and thereby in analysis, it's a necessity to comprehensively outlook the origin, evolution, cumulative trend and precise applications in pharmaceutical analysis. Achieved hereby with chronological and comparative assessment of the studies published pertaining to solubility enhancement of poorly soluble drugs with use of hydrotropic agents alone or in combination for assisting pharmaceutical analysis. The thorough literature searches resulted into 77 references over a span of about 38 years. This comprehensive review critically evaluates existing literature; to our surprise we found Ibuprofen sodium, Lignocaine, Niacinamide and Metformin HCl as atypical hydrotropic agents. We also compared herein mono and mixed approaches which indicated prevalence of mono - hydrotropy over mixed. The possible mechanisms behind solubilization are presented for an additional insight. An essential effort has been made to state arbitrary classification to assist in future applications. The obvious purpose of this study was to collectively evaluate the crucial role of hydrotropic agents in pharmaceutical analyses for better drug delivery. This comprehensive review covers all details since inception to the updates till date which will definitely act as appropriate guideline for pharmaceutical analyst's in need of hydrotropy to assist pharmaceutical analysis for therapies today and tomorrow.
Subject(s)
Pharmaceutical Preparations/chemistry , Chemistry Techniques, Analytical/methods , Drug Industry/methods , Hydrophobic and Hydrophilic Interactions , SolubilityABSTRACT
Hypertension is commonly a quiet condition, and it expands the risk of heart diseases and stroke. Calcium delivers a substantial role in cardiovascular functions and hence is essential for cardiac automaticity and functioning. Calcium channel antagonists are the choice of drugs for the management of cardiovascular diseases; they precisely stop the introduction of calcium through L-type calcium channels are existing channels in the heart. Cilnidipine belongs to the class 4th generation calcium channel blockers as a foremost therapeutic agent used in the treatment of hypertension and heart diseases. This review article focuses on an inclusive account of crucial analytical methodologies used for the pharmaceutical analysis of cilnidipine in pure forms, biological samples and pharmaceuticals. According to literature reports several analytical techniques such as hyphenated techniques, high-performance thin-layer chromatography, high-performance liquid-chromatography, capillary electrophoresis, voltammetry, UV/Vis-spectrophotometry, and Fourier-transform infrared spectroscopy approaches have been used for determination of cilnidipine alone or in the combined dosage form. We have also discussed the pharmacopeial assay methods, physicochemical properties, and also depict the stacked column chart for year wise publication count for cilnidipine. From literature, concluded that the high-performance liquid-chromatography and UV/Vis-spectrophotometry methods are the most prevailing methods for the analysis of cilnidipine. The data presented in this review may provide a very significant base for further studies on cilnidipine in the area of drug analysis.
Subject(s)
Calcium Channel Blockers/analysis , Dihydropyridines/analysis , Animals , Calcium Channel Blockers/pharmacokinetics , Chemistry Techniques, Analytical/instrumentation , Chemistry Techniques, Analytical/methods , Dihydropyridines/pharmacokinetics , Drug Monitoring/instrumentation , Drug Monitoring/methods , Humans , Hypertension/drug therapyABSTRACT
Dapagliflozin (DPG) is a novel drug from class of sodium glucose co-transporter 2 (SGL-2) inhibitors which has been evolved as profound treatment option for the type-2diabetes mellitus (T2DM). Considering the severity of the disease the drug is of crucial significance for the therapy and associated research. As a pharmaceutical dosage form DPG has immense importance as an individual drug and with other antidiabetic drugs as combinations. The drugs existing in combination with DPG are Metformin (MET) and Saxagliptin (SXG). The existence of the Dapagliflozin in combinations further created more interest in reviewing its pharmaceutical, analytical and bio-analytical profile. Such estimations are always in need of precise pharmacological and physicochemical information; hence authors have presented it beforehand. Authors hereby wish to present an essential update pertaining to emergence of gliflozins and DPG. The article further presents a simultaneous and comparative assessment of the analytical investigations published in literature for pharmaceutical estimation to assist future analysis. The thorough literature searches revealed fifty three research papers in total till date. A comprehensive presentation of typical; hyphenated and unique methods used for analysis are outlined effectively. The percentile utilization of analytical approaches since appearance of first publication in 2010 is investigated to report trend in determination. The present review explores the pharmaceutical estimation of DPG to scientifically potentiate analytical research and therapeutic future of DPG as a novel SGL-2 Inhibitor antidiabetic.
Subject(s)
Benzhydryl Compounds/pharmacology , Diabetes Mellitus, Type 2 , Glucosides/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents , MetforminABSTRACT
The obligatory testing of drug molecules and their impurities to protect users against toxic compounds seems to provide interesting opportunities for new drug discovery. Impurities, which proved to be non-toxic, may be explored for their own therapeutic potential and thus be a part of future drug discovery. The essential role of pharmaceutical analysis can thus be extended to achieve this purpose. The present study examined these objectives by characterizing the major degradation products of zileuton (ZLT), a 5-lipoxygenase (5-LOX) inhibitor being prevalently used to treat asthma. The drug sample was exposed to forced degradation and found susceptible to hydrolysis and oxidative stress. The obtained Forced Degradation Products (FDP's) were resolved using an earlier developed and validated Ultra-High-Pressure Liquid Chromatography Photo-Diode-Array (UHPLC-PDA) protocol. ZLT, along with acid-and alkali-stressed samples, were subjected to Liquid-chromatography Mass-spectrometry Quadrupole Time-of-flight (LC/MS-QTOF) studies. Major degradation products were isolated using Preparative TLC and characterized using Q-TOF and/or Proton nuclear magnetic resonance (1HNMR) studies. The information obtained was assembled for structural conformation. Toxicity Prediction using Komputer Assisted Technology (TOPKAT) toxicity analyses indicated some FDP's as non-toxic when compared to ZLT. Hence, these non-toxic impurities may have bio-affinity and can be explored to interact with other therapeutic targets, to assist in drug discovery. The drug molecule and the characterized FDP's were subjected to 3-Dimensional Extra Precision (3D-XP)-molecular docking to explore changes in bio-affinity for the 5-LOX enzyme (PDB Id: 3V99). One FDP was found to have a higher binding affinity than the drug itself, indicating it may be a suitable antiasthmatic. The possibility of being active at other sites cannot be neglected and this is evaluated to a reasonable extent by Prediction of Activity Spectra for Substances (PASS). Besides being antiasthmatic, some FDP's were predicted antineoplastic, antiallergic and inhibitors of Complement Factor-D.
Subject(s)
Drug Contamination , Hydroxyurea/analogs & derivatives , Arachidonate 5-Lipoxygenase/drug effects , Chromatography, Liquid/methods , Computer Simulation , Drug Discovery/methods , Hydrolysis , Hydroxyurea/chemistry , Hydroxyurea/therapeutic use , Hydroxyurea/toxicity , Magnetic Resonance Spectroscopy/methods , Molecular Docking Simulation , Molecular Structure , Oxidative Stress , Software , Tandem Mass Spectrometry/methodsABSTRACT
Acute iron poisoning and chronic iron overload consequences in significant morbidity and mortality worldwide. Treatment of acute iron poisoning and chronic iron overload can be challenging and care providers are often tackled with management dilemmas. Iron chelating agents are commonly prescribed for patients with iron deficiency anemia. In this review article, different analytical techniques are reported used for qualitative and quantitative analysis of iron chelating agents like, deferiprone, deferoxamine, and deferasirox. Efforts are taken to collect all related articles published till October 2018. This review discusses all analytical methods, its advantages and disadvantages as well as its applications. This article will help you to know about basic analytical techniques as well as advanced hyphenated techniques practiced for determination of iron chelating agents in different matrices. The techniques discussed in this review follow the ICH guidelines for method validation.
Subject(s)
Iron Chelating Agents/therapeutic use , Humans , Iron Chelating Agents/pharmacologyABSTRACT
BACKGROUND: Standardization and quality control of homeopathic drugs is very challenging. As mother tinctures are derived from complex natural resources, there is a need of systematic evaluation of chemical markers which correlate with the proposed biological activities of mother tinctures. METHODS: In present study, High-Performance Thin-Layer Chromatography (HPTLC) standardization method of homeopathic mother tinctures of Toxicodendron pubescens using quercitrin and rutin as chemical markers is validated and correlations of content of these markers with its anti-inflammatory effects are established. For HPTLC analysis, precoated silica gel plates were used as stationary phase. Two flavonoids, namely quercitrin and rutin were used as markers. Separation was achieved using methylene chloride:methanol:water:glacial acetic acid (15:1.5:1:8 v/v/v) as mobile phase. The developed plates were scanned at 365 nm. RESULTS: It was observed that quercitrin (Rf value 0.63) and Rutin (Rf value 0.41) are well resolved. The minimum detectable concentrations for quercitrin and rutin were 5 ng/spot. The linearity range was between 100 and 2000 ng/spot for both the markers. Subsequently, anti-inflammatory activity of these formulations was determined against carrageenan-induced paw edema in rats, pain threshold determined by electronic Von-Frey apparatus and paw withdrawal latency (PWL) on hot-plate. All the tested formulations of Rhus Tox showed anti-inflammatory and analgesic activity against carrageenan induced paw edema in rats. Quantitative correlation between the content of markers and anti-inflammatory activity of mother tinctures was established. RESULTS: Anti-inflammatory effect as well as effect on paw withdrawal and pain threshold, at third hour after carrageenan injection, correlated with quercitrin and rutin content in the respective formulations. CONCLUSIONS: This study validates a quantitative HPTLC method for standardization of homeopathic mother tincture of Rhus Tox and establishes quercitrin and rutin as markers corresponding its biological activity. Contents of quercitrin and rutin in T. pubescens mother tincture correlates with its anti-inflammatory and analgesic actions and the validated HPTLC method can be used in standardization of homeopathic mother tincture of T. pubescens.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Flavonoids/therapeutic use , Plant Extracts/pharmacology , Toxicodendron , Animals , Biomarkers, Pharmacological , Carrageenan/adverse effects , Disease Models, Animal , Homeopathy/methods , Male , Phytotherapy/methods , Rats , Rats, WistarABSTRACT
A new stability-indicating reversed-phase high-performance thin-layer chromatographic (RP-HPTLC) method for densitometric analysis of thiocolchicoside was developed and validated. The chromatograms were developed using aluminum plates pre-coated with silica gel 60 RP-18 F254S as a stationary phase and methanol : water (70 : 30 v/v) as a mobile phase. The compact band for thiocolchicoside was observed at R f value of 0.60 ± 0.02 at an absorption wavelength of 377 nm. The linear regression data for the calibration plots (r (2) = 0.9984) was found with respect to peak area in the concentration range of 100-600 ng per band. The limit of detection (LOD) and limit of quantification (LOQ) were 9.77 ng and 29.63 ng, respectively. The drug was exposed to acidic and alkaline hydrolysis, oxidation, photo degradation, and dry heat conditions. The peaks of degradation products were well-resolved from the peak of the standard drug with significantly different R f values. Statistical analysis proved that the established RP-HPTLC method is reproducible, selective, and accurate for the determination of thiocolchicoside in its formulations. The method can effectively separate the drug from its degradation products, and it can be considered as stability-indicating assay.
ABSTRACT
A series of 6-bromo-2-ethyl-3-(substitutedbenzo[d]thiazol-2-yl)quinazolin-4(3H)-one 3 (a-j) were synthesized using appropriate synthetic route and evaluated experimentally by the Maximal Electro Shock (MES) and the PTZ-induced seizure methods. Among the tested compounds, 3-(benzo[d]thiazol-2-yl)-6-bromo-2-ethylquinazolin-4(3H)-one (3a) has shown significant activity against tonic seizure by the MES model and 6-bromo-2-ethyl-3-(6-methoxybenzo[d]thiazol-2-yl)quinazolin-4(3H)-one (3h) against clonic seizure by PTZ-induced seizure model. Not one of the selected compounds demonstrated any sign of neurotoxicity and hepatotoxicity.
Subject(s)
Anticonvulsants/chemistry , Anticonvulsants/pharmacology , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Quinazolines/chemistry , Animals , Anticonvulsants/chemical synthesis , Anticonvulsants/toxicity , Benzothiazoles/chemical synthesis , Benzothiazoles/toxicity , Drug Design , Electroshock/adverse effects , Male , Mice , Pentylenetetrazole/adverse effects , Seizures/chemically induced , Seizures/drug therapy , Seizures/enzymologyABSTRACT
CONTEXT: This study evaluated the in vitro and in vivo antidiarrheal activity, oral acute toxicological profile, and developed a chemical fingerprint of Berberis aristata Linn. (Berberidaceae). MATERIALS AND METHODS: The ethanol (by maceration) and aqueous (by Soxhlet) extracts of Berberis aristata bark were used for the study. The study involved the antimicrobial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) by micro dilution) and antidiarrheal (castor oil induced diarrhea, charcoal motility) tests. The active principle, berberine was characterized by different spectroscopic and chromatographic techniques. RESULTS: The MIC and MBC (of both extracts) against all strains of Shigella were recorded between 125 to 500 µg/mL and 300 to 600 µg/mL, respectively. The MIC and MBC values of berberine are almost comparable to standard ciprofloxacin. UV and IR spectroscopy along with HPTLC and HPLC studies showed presence of berberine in the extracts. The onset of castor oil induced diarrhea was delayed and number of diarrheal episodes was reduced by both the extracts in a dose dependent manner. Similarly, the length of intestine traveled by the feed was also significantly reduced in the charcoal motility test by both the extracts. LD(50) of >5000 mg/kg body weight was observed for both extracts in the acute oral toxicity studies with Swiss albino mice. CONCLUSION: The results validate in vivo and in vitro antidiarrheal activity of Berberis aristata extracts and provide its chemical fingerprint.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antidiarrheals/pharmacology , Berberis/chemistry , Plant Extracts/pharmacology , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/toxicity , Antidiarrheals/administration & dosage , Antidiarrheals/toxicity , Berberine/isolation & purification , Berberine/pharmacology , Ciprofloxacin/pharmacology , Diarrhea/drug therapy , Disease Models, Animal , Dose-Response Relationship, Drug , Lethal Dose 50 , Mice , Microbial Sensitivity Tests , Plant Bark , Plant Extracts/administration & dosage , Plant Extracts/toxicity , Shigella/drug effects , Toxicity Tests, AcuteABSTRACT
Atorvastatin calcium is a synthetic HMG-CoA reductase inhibitor that is used as a cholesterol-lowering agent. A simple, sensitive, selective, and precise RP-HPTLC-densitometric determination of atorvastatin calcium both as bulk drug and from pharmaceutical formulation was developed and validated according to International Conference on Harmonization guidelines. The method used aluminum sheets precoated with silica gel 60 RP18F254S as the stationary phase, and the mobile phase consisted of methanol-water (3.5 + 1.5, v/v). The system gave a compact band for atorvastatin calcium with an Rf value of 0.62 +/- 0.02. Densitometric quantification was carried out at 246 nm. The linear regression analysis data for the calibration plots showed a good linear relationship with r = 0.9992 in the working concentration range of 100-800 ng/band. The method was validated for precision, accuracy, ruggedness, robustness, specificity, recovery, LOD, and LOQ. The LOD and LOQ were 6 and 18 ng, respectively. The drug underwent hydrolysis when subjected to acidic conditions and was found to be stable under alkali, oxidation, dry heat, and photodegradation conditions. Statistical analysis proved that the developed RP-HPTLC-densitometry method is reproducible and selective and that it can be applied for identification and quantitative determination of atorvastatin calcium in bulk drug and tablet formulation.
Subject(s)
Chromatography, Thin Layer/methods , Densitometry/methods , Heptanoic Acids/analysis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/analysis , Pyrroles/analysis , Atorvastatin , TabletsABSTRACT
A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for densitometric determination of nebivolol hydrochloride both as a bulk drug and in formulation was developed and validated as per the international conference on harmonization guidelines (ICH). The method employed TLC aluminium plates precoated with silica gel 60F254 as the stationary phase. The solvent system consisted of toluene-methanol-triethylamine (3.8:1.2:0.2 v/v/v). Densitometry analysis of nebivolol hydrochloride was carried out in the absorbance mode at 281 nm. The system was found to give compact spot for nebivolol hydrochloride (R(f) value of 0.33 +/- 0.02). The linear regression analysis data for the calibration plots showed good relationship with r(2)= 0.9994 +/- 0.0002 in the concentration range 500-3000 ng/spot. The mean value +/- SD of slope and intercept were 3.761 +/- 0.017 and 127.39 +/- 19.53 with respect to peak area. The limits of detection (LOD) and limit of quantitation (LOQ) were 63.10 ng/spot and 191.23 ng/ spot, respectively. Nebivolol hydrochloride was subjected to acid and alkali hydrolysis, oxidation, thermal degradation, and photodegradation. All the peaks of degradation products were well-resolved from the standard drug with significantly different R(f) values. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of nebivolol hydrochloride in the bulk and pharmaceutical dosage form.