Analytical methods drug administration

The administration of some drugs for prophylactic and enhanced production purposes requires a period of withdrawal prior to slaughter of the animals and suitable analytical methods to ensure that their products are acceptable as food (Table... 

The Pesticide Analytical Manual of the US Food and Drug Administration or the Official Methods of Analysis of AOAC International are method collections with international recognition. Both compilations are written in English, one prerequisite for its success. Method collections of EU Member States are most often available only in the national languages. Eor this reason, they are relatively unknown in other Member States. Fortunately, some good collections of official national methods are translated into the English language. The most important are... 

Pesticide Analytical Manual. Volume 1, Multiresidue Methods, third edition, US Food and Drug Administration Washington, DC, Sect. 302 (1994). 

Guideline for Submitting Samples and Analytical Data for Methods Validation, February 1987, Center for Drugs and Biologies, Food and Drug Administration, Rockville, MD. 

After oral administration of 400 mg of rifaximin to fasted healthy volunteers blood drug concentration was found to be lower than the detection limit of the analytical method (i.e. 2.5 ng/ml) in half of them [102]. In the remaining subjects very low amounts were detected at some of the time intervals during the first 4 h after intake. Along the same lines, the urinary concentrations of the drug were very low and often undetectable. The effect of food on the absorption of the antibiotic was also evaluated [34] and a significant, albeit not clinically relevant, increase of bioavailabity was observed after a high-fat breakfast (table 5). 

FDA. 1994b. 302 and 303 Methods for nonfatty foods. In Pesticides Analytical Manual, 3rd edition, vol. 1 Multiresidue methods. US. Department of Health and Human Services, Food and Drug Administration. 

U.S. Food and Drug Administration (FDA) (2000), Guidance for industry, Analytical procedures and methods validation—Chemistry, manufacturing, and controls documentation, FDA, Rockville, MD. 

During the 1990 Washington Conference on Analytical Methods Validation Bioavailability, Bioequivalence and Pharmacokinetic Studies [1], parameters that should be used for method validation were defined. The final report of this conference is considered the most comprehensive document on the validation of bioanalytical methods. Many multinational pharmaceutical companies and contract research organizations contributed to its final draft. This scientific meeting was sponsored by the American Association of Pharmaceutical Scientists (AAPS), the Association of Official Analytical Chemists (AOAC), and the U.S. Food and Drug Administration (FDA). The conference report has been used as a reference by bioanalytical laboratories and regulatory agencies worldwide. 

Generation of potential human metabolites for structural identification prior to administration of the drug candidate to humans can be performed with either cDNA-expressed enzymes or tissue fractions. This allows identification of potential human metabolites and development of appropriate analytical methods prior to clinical trials. Generation and identification of pharmacologically active human metabolites early in the development process can be beneficial for obtaining appropriate patent protection. 

Quality criteria for quantitative analytical methods, in general, have been proposed or arc lo be proposed by several international organizations including the Association of Official Analytical Chemists, the Food and Drug Administration, the Codex Committee for Residues of Veterinary Drugs in Food, the International Dairy Federation, and the European Union. The European Union, in particular, has laid down minimum quality criteria for quantitative drug residue methods,... 

United States Food and Drug Administration (1987) Acrylonitrile. In Fazio, T. Sherma, J., eds, Food Additives Analytical Manual, Vol. 11, A Collection of Analytical Methods for Selected Food Additives, Arlington, VA, Association of Official Analytical Chemists, pp. 1-24... 

Any analytical method should be validated. The U.S. Food and Drug Administration has proposed guidelines on submitting samples and analytical data for validation (78). In LC one should check at least specificity, selectivity, accuracy, precision, linearity, reproducibility, limit of detection, limit of quantitation, and robustness. 

Low-dose regimens frequently result in very low corticosteroid concentrations in body fluids (e.g., low pg/mL range in plasma). PK analysis that is often necessary to manage these therapies is hindered by the inadequate sensitivity by most established analytical methods. In addition, certain drug delivery strategies, such as inhalation or intraocular injection, result in systemic levels too low to be detected by current methods. Furthermore, administration of some corticosteroid prodrugs, such as these in the forms of acetates/propionate, often results in sustained, low concentrations in plasma. Therefore, a highly sensitive and selective analytical approach is necessary for cases in which sustained low concentration of corticosteroids may be present systemically or in tissues. 

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