Mi grado c.l.e.i. 6-2

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Leonardo Vasquez

Education

CONGRATULATIONS…
GRACIAS…
COL. BOSQUES DEL NORTE…
C.L.E.I. 6-2

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biotransformation of drug Biotransformation/Xenobiotic metabolism/ drug metabolism/detoxification. -Xenobiotics: a wide variety of foreign compounds to which humans get exposed in day to day life. -It includes unknown compounds, drugs, environmental pollutants, toxins. -Many xenobiotics can evoke biological responses. DEFINITION The biochemical alteration of drug or xenobiotic in the presence of various enzymes that acts as a catalyst which themselves not consumed in the reaction and there by may activate or deactivate the drug is called biotransformation. Why Biotransformation is necessary?: To easily eliminate the drug To terminate drug action by inactivating it Consequences of Biotransformation Active to Inactive: Phenobarbitone---- Hydroxyphenobarbitone Inactive (prodrug) to Active : L-Dopa ---- Dopamine Parathion -- Paraoxon Talampicillin -- Ampicillin Active to equally active: Diazepam -- Oxazepam Amitriptyline -- Nortriptyline Imipramine -- Des-imipramine Codeine -- Morphine Sites of biotransformation In the body: Liver, small and large intestines, lungs, skin, kidney, nasal mucosa & brain. Liver is considered “metabolite clearing house” for both endogenous substances and xenobiotics. Intestines are considered “initial site of drug metabolism”. FIRST PASS METABOLISM: First pass metabolism or presystemic metabolism or ‘first pass effect’ After oral administeration many drugs are absorbed from the small intestine - transported first via portal system to the liver, where they undergo extensive metabolism before reaching systemic circulation. fundamental concepts in drug biotransformation Lipid soluble drugs are poorly excreted in the urine. They tend to store in fat and/or circulate until they are converted (phase I biotransformation) to more water soluble metabolites or metabolites that conjugate (phase II biotransformation) with water soluble substances. Water soluble drugs are more readily excreted in the urine. They may be metabolized, but generally not by the CYP enzyme systems. Enzymes catalyzing phase I biotransformation reactions Enzymes catalyzing phase I biotransformation reactions include: cytochrome P-450 aldehyde and alcohol dehydrogenase deaminases esterases amidases epoxide hydratases Addition of water Cleavage of R-O or R-N bond accompanied by addition of H2O CYTOCHROME P450 The cytochrome P-450 families are referred to using an arabic numeral, e.g., CYP1, CYP2, etc. Each family has a number of subfamilies denoted by an upper case letter, e.g., CYP2A, CYP2B, etc. The individual enzymes within each subfamily are denoted by another arabic numeral, e.g., CYP3A1, CYP3A2, etc.

METABOLISM

Nihal Calicut

Pak china relation s.....

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an overview of lcms and gcms and its applications.... LC-MS: It is the combination of liquid chromatography and the mass spectrometry. * In LC-MS we are removing the detector from the column of LC and fitting the column to interface of MS. * In the most of the cases the interface used in LC-MS are ionization source INTERFACE Apart from being an inlet system for the MS, an LC–MS interface is also the coupling of a detector (MS) to a chromatograph. The choice of LC–MS interface strongly influences the characteristics of the MS as a detector for LC. Therefore, we should keep in mind what characteristics are ideal for an LC detector 1. Direct liquid introduction (DLI): The DLI interface was developed in order to solve the problems with in-capillary evaporation in the capillary inlet. In a DLI interface, the column effluent is nebulized by the disintegration into small droplets of a liquid jet formed at a small diaphragm After desolvation of the droplets in a desolvation chamber, the analytes can be analysed using solvent-mediated CI with the LC solvents as the reagent gas. Advantages: • No heat is applied to the interface and it is therefore able to deal with thermally labile materials better than the moving-belt interface. • The interface contains no moving parts and is cheap and simple to construct and operate and is inherently more reliable than the moving-belt interface. • Both positive- and negative-ion CI spectra can be generated and the interface provides molecular weight information, plus it can also be used for sensitive quantitative and semi-quantitative procedures. Disadvantages: • Involatile compounds are not usually ionized with good efficiency. • The pinhole is prone to blockage and therefore the system must be kept completely free of solid materials. • Only a small proportion of the flow from a conventional HPLC column is able to enter the source of the mass spectrometer and sensitivity is consequently low 2. Moving belt/wire: In a moving-belt interface (MBI), the column effluent is deposited onto an endless moving belt from which the solvent is evaporated by means of gentle heating and efficiently exhausting the solvent vapours. After removal of the solvents, the analyte molecules are (thermally) desorbed from the belt into the ion source and mass analysed. The MBI for LC.MS was used in a wide variety of applications, including the analysis of drugs and their metabolites, pesticides, steroids, alkaloids, polycyclic, aromatic hydrocarbons and others. Advantages: • The interface can be used with a wide range of HPLC conditions. • The analyst does have some choice of the ionization method to be used; EI, CI and FAB are available, subject to certain limitations, and thus both molecular weight and structural information may be obtained from the analyte(s) under investigation.

Lcms gcms and its applications

Nihal Calicut

Electrical, Electronics and Computer Engineering, Information Engineering and Technology, Mechanical, Industrial and Manufacturing Engineering, Automation and Mechatronics Engineering, Material and Chemical Engineering, Civil and Architecture Engineering, Biotechnology and Bio Engineering, Environmental Engineering, Petroleum and Mining Engineering, Marine and Agriculture engineering, Aerospace Engineering.

International Journal of Engineering Research and Development

IJERD Editor

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Mi grado c.l.e.i. 6-2

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18. CONGRATULATIONS… GRACIAS… COL. BOSQUES DEL NORTE… C.L.E.I. 6-2

Mi grado c.l.e.i. 6-2

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