Plasmid vaccination is a smart gene delivery application mostly achieved through the utilisation of viral or copolymeric systems as surrogated carriers in micro or nano formulations. A common polymeric protocol for plasmid vaccine formulation, which as somewhat been successful, is via the complexation of the DNA molecules with a cationic polymer, and encapsulating in a vehicular carrier polymer. Even though plasmid vaccination research has not witnessed the much anticipated success, due a number of cellular and physicochemical reasons, application of copolymeric carriers with tight functionalities is a promising strategy to optimally deliver the DNA molecules; in view of the available chemistries and physical properties that could be tuned to enable enhanced targeted delivery, uptake and specific transfection. This also enables the targeting of specific epitopes and antigen presenting cells for the treatment of many pathogenic infections and cancer. This paper provides a brief critical review of the current state of plasmid vaccines formulation and molecular delivery with analysis of performance data obtained from clinical trials.

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Pharmaceutical drug development is a complex and lengthy process, requiring excellent project and laboratory management skills. Bioanalysis anchors drug safety and efficacy with systemic and site of action exposures. Development of scientific talent and a willingness to innovate or adopt new technology is essential. Taking unnecessary risks, however, should be avoided. Scientists must strategically assess all risks and find means to minimize or negate them. Laboratory Managers must keep abreast of ever-changing technology. Investments in instrumentation and laboratory design are critical catalysts to efficiency and safety. Matrix management requires regular communication between Project Managers and Laboratory Managers. When properly executed, it aligns the best resources at the right times for a successful outcome. Attention to detail is a critical aspect that separates excellent laboratories. Each assay is unique and requires attention in its development, validation and execution. Methods, training and facilities are the foundation of a bioanalytical laboratory.

Methods started in discovery are optimized as they progress through preclinical and clinical development. Making a robust assay includes testing individual steps for consistency and points of failure. Assays may be transferred, optimized and revalidated several times. A rugged assay will not only meet regulatory requirements, but will execute with a low failure rate and confirm results under repeat analysis. Challenging aspects such as differential recovery, sample stabilization, resolution of isomers or conjugate analysis must be tackled and made routine. The proper selection of the IS can overcome limitations. It is best to know the potential points of failure before a study has started, but lessons learned from each study also provide invaluable insights to improve assay ruggedness.

Aim: Stability must be evaluated before quantitation of drugs or metabolites concentrations in biological matrices. We reported a case study where instability of a drug metabolite was mediated by hemolysis. Materials & methods: The instability of both enantiomers of N-desethyloxybutynin was observed in hemolyzed plasma stored at -20°C. The investigations indicated that heme-mediated oxidation converted the metabolite to its N-oxide. Storing samples under lower temperature (-50°C or below) or treatment with the antioxidant ascorbic acid stabilized the metabolite. Conclusion: The evaluation of the stability of some analytes in a hemolyzed sample is crucial as it may negatively impact incurred sample reanalysis or pharmacokinetic profiles on highly hemolyzed samples.