The field of bioanalytical chemistry, or bioanalysis, is an important area of research that has a direct impact on the work of pharmacokineticists. Essentially, bioanalysis converts a blood sample (or any other matrix) into a drug concentration by the use of analytical equipment. Over the next few weeks, I would like to cover a variety of topics related to bioanalysis that should be of interest to individuals in the field of pharmacokinetics. After all, bioanalysis results are the starting materials for pharmacokinetic analysis. Just as any good cook wants to use the best ingredients to make a delicious meal, so too must the pharmacokineticist select the best bioanalysis methodologies and tools to ensure the highest quality pharmacokinetic analysis.
First, I would like to help define the term bioanalysis or bioanalytical chemistry. The field of bioanalysis grew out of the analytical chemistry field where chemicals and chemical structures are identified using a collection of tools. The analytical chemistry field is designed to accurately and precisely identify the identity and quantity of a chemical in a sample. Generally, analytical chemistry uses something called a “neat solution”. A neat solution generally refers to a single chemical dissolved in a single solvent. The solvent can be aqueous or organic, but it is usually homogeneous. As an example, consider NaCl in water (ie, salt water). The Na and Cl ions are dissolved and dissociated in the water. The analytical chemist can then take a sample of the water and use appropriate techniques to identify the presence of Na and Cl, and then identify the amount of Na and Cl in the sample. These analytical chemistry tools are used in the pharmaceutical industry during drug discovery, medicinal chemistry, formulation, and manufacturing. As the pharmaceutical industry developed, there was interest in measuring drug content in biological samples (blood, serum, plasma, cerebrospinal fluid, muscle, brain, etc.). Research scientists from the analytical chemistry groups began to apply their methodologies of analytical chemistry to biological samples. Thus was born the field of biological analytical chemistry, or as it is now known, bioanalytical chemistry or bioanalysis for short.
There are numerous techniques (probably more than I can name!) used to detect and measure drug levels in biological samples. The techniques, specificity, precision, sensitivity, and accuracy continue to improve as research is advanced in methodologies and equipment. Therefore, my reviews and comments may not apply to every technique, but I hope to provide a basic overview of the field of bioanalysis and what things you as a pharmacokineticist might want to consider. In this overview, I will touch on several common techniques used in bioanalysis along with other more specialized methods. At the end of this series of posts, I hope you have a better understanding of bioanalysis and the science behind measuring drug levels in biological samples.
Let’s begin with a basic overview of the bioanalytical process:
- Biological sample is obtained from an organism. Common samples include blood, plasma, serum, cerebrospinal fluid, urine, and tissues.
- The biological sample is processed to remove endogenous substances, matrix components (eg, proteins), and other chemicals that will interfere with sample analysis. In essence, the purpose is to extract all of the drug from the biological sample into a neat solution for analysis.
- The neat solution is analyzed with an appropriate detection method that has been calibrated with known samples. The response from the unknown sample is compared to the known samples and the concentration is estimated, accounting for dilutions and other manipulations during sample preparation.
Those may seem overly simplistic, but those are the three steps used in almost every bioanalysis method. Of course, what you read as a simple step may require a significant amount of work and expertise in the real world; however, those three basic steps are the foundation of bioanalysis. In essence, Step 3 is very similar to analytical chemistry work. Steps 1 and 2 simply convert a biological sample into a neat solution.
In subsequent posts, I will discuss specific bioanalysis methods and procedures. I look forward to sharing this with you and welcome any comments about the type of information you would like to see.
The approved drug label is the official description of a drug product and includes what the drug is used for, who should take it, side effects, instructions for use, and safety information for clinicians and patients. For drug companies, the label is the culmination of years of work and millions, if not billions of dollars. Every element, word, and comma in the label will impact the potential patient population that can benefit from that new drug, while detailing any associated risks, including staying “silent” when information is not available. In other words, what is included or excluded from the label will affect the overall profit potential of the drug.
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