Quality control Bioanalysis

A typical application of GC to the determination of a drug in plasma is in the determination of the anti-epileptic drug valproic acid after solid phase extraction (see Ch. 15) by GC with flame ionisation detection. In this procedure, caprylic acid, which is isomeric with valproic acid, was used as an internal standard. The limit of detection for the drug was 1 pg/ml of plasma. The trace shown in Figure 11.25 indicates the more extensive interference from background peaks extracted from the biological matrix which occurs in bioanalysis compared to the quality control of bulk materials. 

Due to the differences between spiked samples (calibration standards and quality controls) and incurred samples as well as the potential inter sample differences, variations in internal standard response during incurred sample analysis are somewhat expected and they should be monitored with predetermined criteria to identify any potential bioanalysis abnormality. Many different factors (not necessarily only matrix effect) could cause variations in internal standard responses during incurred sample analysis. The same phenomenon, e.g., consistently higher IS responses for all the samples of a subject, can be caused by different reasons. Accordingly, each case should be dealt with individually with an open mind. 

Inherent to macromolecules is the associated variability (i.e., glycosylation and deamidation) of the material from different preparations. Therefore, it is not usually feasible to obtain a reference standard for a macromolecule drug for use in bioanalysis. Typically, what is obtained is a well-characterized product. Therefore, it is important to clearly state the source of the material and to refer to any documentation describing characteristics of that material. Whenever possible, the standards, the validation samples, and quality control (QC) samples should be prepared from separate vials of the same source material. In the case of lyophilized material, it is preferred to reconstitute two separate vials to prepare standards and QCs. In... 

With the increasing number, diversity, and complexity of compounds being analyzed, UPLC presents the possibility to extend and expand the utility of separation science. Today, UPLC is widely used for metabolite identification analysis of natural products and herbal medicines pharmacokinetic, toxicity, degradation, bioanalysis, and bioequivalence studies quality control and in drug discovery determination of pesticides and separation of various pharmaceutical-related small organic molecules, proteins, and peptides. UPLC is also used for impurity profiling, method development, and validation performed in quality assurance and quality control laboratories [46,47,56-69]. 

Strictly speaking, bioanalysis is about the demonstration, not the presumption, of quality. The pace of the drug-discovery research environment does not allow for excessive controls over quality assurance. In many settings, few if any guidelines may be warranted. In this subsection, the common pitfalls of LC-MS/MS-based bioanalysis are briefly discussed to provide insight into factors that affect precision and accuracy. 

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