Development and validation of lc ms ms methods for pharmacokinetic evaluation of diltiazem and acamprosate calcium in human plasma

Abstract

In the United States, the food, drugs and cosmetic act of 1938 and the newlineKefauver Harris amendment to this act in 1962 required that the safety and newlineefficacy data be generated to support claims for active ingredient(s) in the drug newlineproduct before approval for sale. In the last several decades, the food and drug newlineadministration has allowed the substitution of one formulation with another newlinewithout requirement to repeat expensive and time consuming safety and newlineefficacy studies. The scientific rationale for these judgments was that a set of newlinebiopharmaceutic, pharmacokinetic and statistical standards can be established newlineto document that the test formulation is therapeutically interchangeable with the newlinereference formulation, in the absence of clinical trials. newlineA test formulation that meets this criterion is termed to be bioequivalent to and newlinetherapeutically interchangeable with the reference formulation. These criteria newlineare also applicable when the marketed formulation is reformulated for newlinemanufacturing and marketing reasons, newline1. The product documentation criteria requires that the new formulation must newlinecontain the same active ingredients in the same dose form and strength, is newlineintended for the same dose form and strength and is labeled comparably newlinewith the formulation it is designed to replace. newline2. The manufacturing documentation criteria related to the manufacturing newlineprocesses ensures that the drug products exhibit known and consistent newlinestability, purity and potency. newline3. A final requirement for determination of equivalence between one newlineformulation and the other is usually an in vivo bioequivalence study to newlineconfirm that the levels of the drug/metabolite in the selected biological fluids newlineare comparable after administration of each formulation.