ICBio Clinical Research Pvt Ltd
common method with atorvastatin
common method with ezetimibe
common method with ezetimibe glucuronide
common method with simvastatin
What is Ezetimibe?
Ezetimibe is an anti-hyperlipidemic medication which is used
to lower cholesterol levels. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epitheli What is bioanalytical method development and validation? Bioanalytical Method Validation, the term validation means the action of checking or proving the validity or accuracy of something. (BMV) guidelines for Ezetimibe are applied to bioanalytical methods that are used for the quantitative determination of Ezetimibe and its metabolites in biological matrices such as plasma, urine and preclinical studies and also for bioanalytical method validation for small molecules. A compound can often be measured by several methods and the choice of analytical method involves many considerations. Analysis of drugs and their metabolites in a biological matrix is carried out using different extraction techniques like liquid-liquid extraction, solid phase extraction (SPE) and protein precipitation from these extraction methods samples are spiked with calibration (reference) standards and using quality control (QC) samples. These bioanalytical validations play a significant role in evaluation and interpretation of bioavailability, bioequivalence, pharmacokinetic, and toxicokinetic studies. In which different parameters like accuracy, precision, selectivity, sensitivity, reproducibility, and stability are performed. Bioanalytical Method Development & Validation Service providers CROs / CDMOs have vast experience in Validated methods for Active Pharmaceutical Ingredients (APIs) for a variety of platforms including HPLC( High Performance Liquid Chromatography), RP-HPLC (Reverse Phase- High Performance Liquid Chromatography), RP-UPLC (Reverse Phase- Ultra Performance Liquid Chromatography), LC/MS/MS, GC/MS or GC/FID, ICP/MS, and ligand binding assays (ELISA or other cell-based assays). As both an in vivo and analytical CRO, they support bioanalytical method development & validation services of a variety of Active Pharmaceutical Ingredients (APIs) / Drugs. Bioanalytical studies for Ezetimibe are typically conducted under GLPs, where product release and stability tests follow GMP quality requirements. Limit Of Quantification (LOQ) Lower limit of quantification The LLOQ is the lowest amount of an analyte in a sample that can be quantitatively determined with suitable precision and accuracy (bias). There are different approaches to the determination of LLOQ. LLOQ based on signal to noise ratio (S/N): This approach can only be applied if there is baseline noise, for example, to chromatographic methods. Signal and noise can then be defined as the height of the analyte peak (signal) and the amplitude between the highest and lowest point of the baseline (noise) in a certain area around the analyte peak. For the LLOQ values of Ezetimibe, S/N is usually required to be equal to or greater than 10. The estimation of baseline noise can be quite difficult for bioanalytical methods, if matrix peaks elute close to the analyte peak. Upper limit of quantification The upper limit of quantification (ULOQ) is the maximum analyte concentration of a sample that can be quantified with acceptable precision and accuracy (bias). In general, the ULOQ value of Ezetimibe is identical with the concentration of the highest calibration standard. Bioanalytical techniques used in Validation of Ezetimibe: Commonly used Bioanalytical chromatographic methods in bioanalytical studies for Ezetimibe are as follows: Hyphenated techniques: A hyphenated technique is combination or coupling of two different analytical techniques with the help of proper interface. Mainly chromatographic techniques are combined with spectroscopic techniques, For e.g. LC–MS (liquid chromatography–mass spectrometry); GC–MS (gas chromatography–mass spectrometry); CE–MS (capillary electrophoresis–mass spectrometry) Liquid Chromatography-Mass Spectrometry (LC-MS/MS or LC-MS-MS): Bioanalytical liquid chromatography-mass spectrometry or Bioanalytical Mass Spectrometry is a technique that uses liquid chromatography with the mass spectrometry. LC-MS or LC-MS-MS and rapid and sensitive high performance LC/MS/MS method is commonly used in laboratories for the quantitative and qualitative estimation of Ezetimibe and other drug products and biological samples. LC-MS has played an important role in evaluation and interpretation of bioavailability, bioequivalence and pharmacokinetic details of Ezetimibe. Through LC-MS biological samples are determined throughout all phases of method development of a Ezetimibe and its salts in research and quality control. HPLC (high performance liquid chromatography) & Gas chromatography are also important for the analysis. New Analytical Method Development: Method of analysis are being consistently developed, improved, validated, collaboratively studied and applied and also new analytical method has been developed. Chromatographic separations along with RP-HPLC and RP-UPLC method are considered as rapid stability indicating methods which depend on the samples to be analyzed. The chromatographic procedure is important for the systemic approach to LC-MS/MS method development. In most cases as desired separation can be achieved easily with only a few experiments. In other cases a considerable amount of experimentation may be needed. Reversed Phase Chromatography: Reversed phase packings such as C18, C8 are the most popular and most extensively used for Reversed Phase Chromatography . In addition to these C4, C2 and phenyl bonded are also available. Reversed phase sorbents usually involves conditioning with an organic solvent (e.g. methanol) followed by an aqueous solvent (e.g. water). Normal Phase Chromatography: Normal phase packings include silica, amino and alumina. Normal phase packing generally requires conditioning with a non polar solvent and elution is carried along with polar solvents. Compounds which have basic pH functional groups are retained by silica. However, polar compounds are irreversibly retained on a silica surface and in this case amino may be used. GAS CHROMATOGRAPHY-MASS SPECTROMETRY (GC-MS) Gas chromatography–mass spectrometry (GC-MS) is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different Ezetimibe salts within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation, and Method Validation of Ezetimibe and other drug products. The fundamental bioanalytical method validation parameters include precision and accuracy, sensitivity. Another innovative bioanalytical technique is solid phase extraction bioanalysis or SPE bioanalysis. There are many optimisation and validation studies have been carried out for the assessment of SPE for Ezetimibe. A sensitive, specific bioanalytical method provided by Bioanalytical Service Providers are critical for a reliable pharmacokinetic experiment. It involves Comparative assessment of bioanalytical method validation several different techniques such as Method Transfer, Partial Validation, and Cross Validation of bioanalytical methods and other Chromatographic techniques, especially, high performance liquid chromatography (HPLC) coupled with different detection systems like LC-MS/MS bioanalysis method development, validation, and sample analysis and RP-HPLC and RP-UPLC techniques are some of the preferred techniques, routinely employed in bioanalytical laboratories as compared to any other method of analysis owing to their precision, accuracy, reliability and applicability to large-scale analysis. The goal is to determine whether the obtained data for Ezetimibe are comparable. Cross validation assay and also include method transfer techniques consists of analysis of quality control samples (either spiked, incurred samples, or both), assayed under the different experimental conditions or different sites with validated methods of Ezetimibe, as appropriate. The same set of samples for Ezetimibe should be measured by both analytical sites or using the two different Bio-analytical methods. It is desirable that cross validation should be performed in advance of study samples being analyzed. It is recommended that the following rationale should be used in deciding how best to perform the cross validation. QbD (Quality By Design) development bioanalytical method is a novel method for the analysis of drug products extensively used in the industries. High performance liquid chromatography is one of the most accurate methods widely used for the quantitative as well as qualitative analysis of Ezetimibe and is used for determining Ezetimibe stability. Stability indicating HPLC methods are used to separate various drug related impurities that are formed during the synthesis or manufacture of Ezetimibe . This article discusses the strategies and issues regarding the development of stability indicating HPLC system for Ezetimibe given by Bioanalytical Service Providers. A number of key chromatographic factors were evaluated in order to optimize the detection of all potentially relevant degradants.For Example: Analytical QbD-based systematic bioanalytical HPLC method and HPLC-PDA for bioanalytical method along with RP-HPLC-PDA method . The method should be carefully examined for its ability to distinguish Ezetimibe from the impurities. Several drug products have been tested using analytical method and validation using HPLC/PDA. New chemical entities and drug products such as Ezetimibe must undergo forced degradation studies which would be helpful in developing and demonstrating the specificity of such stability indicating methods. At every stage of drug development practical recommendations are provided which will help to avoid failures. HPLC is a popular technique as Bioanalytical Service Providers for monitoring the decrease in Ezetimibe and corresponding increase in degradation products due to its separating abilities. Stress Degradation HPLC is also one such novel technique. However, the HPLC method must be developed carefully to ensure that degradation products of Ezetimibe are both separated and detected appropriately. A stability indicating analytical method (SIAM) is a validated analytical procedure that is provided under contract bioanalytical services of Ezetimibe which are accurately and precisely measures active ingredients (Ezetimibe) free from potential interferences like degradation products, process impurities, excipients, or other potential impurities, and the FDA recommends that all assay procedures for stability studies be stability indicating. It is recommended that forced degradation test or chemical stress or stress degradation studies can be carried out to determine if analytical methods are stability indicating prior to embarking on long term stability studies. There are various stress testing analytical methods and techniques including stress testing bioanalytical methods, stress testing bioanalysis and also stress testing chromatography. There are also several method and development and validation techniques for UV- Visible Spectrophotometric technique. The lower limit of quantification (LLOQ) is the lowest concentration of analyte in a sample which can be quantified reliably, with an acceptable accuracy and precision. The LLOQ is considered being the lowest calibration standard (see Accuracy and Precision). In addition, the analyte signal of the LLOQ sample should be at least 5 times the signal of a blank sample. The LLOQ should be adapted to expected concentrations and to the aim of the s