A Toxicological Perspective On Detecting Drugs And Metabolites In Biological Matrices

Most critical objectives associated with the investigational procedures of both the toxicological and pharmaceutical drugs is their extraction from their biological matrices. For the past three decades, the analytical instrumentation industry has witnessed a lot of advancements. SPE or liquid-liquid extraction methods have been widely employed in the processes related to the extraction of the active ingredient, its purification and subsequent enrichment.

Toxicological studies represent the entire frame of the analytical process through which the presence or absence of the toxic substance is determined within an analysed sample. This includes estimation of the physicochemical methods for isolating, identifying, and quantifying the presence of toxic substance across different environmental components. ADME/PK analysis usually is employed in the determining both the absorption as well as metabolism. This analysis has become an integral part of the drug research process as any inadequacy detected either in the metabolism or the pk assessment results in NCE failure.

Fortunately, the current efforts invested throughout the drug discovery and development process have re-directed their focus on the process of identification of metabolism and pharmacokinetic issues at the earliest possible stage. This helps in reducing the attrition value of potent drug candidates throughout the developmental stage. A drug’s metabolic fate can be held responsible for problems associated with the factors related to bioavailability, drug-drug interactions, toxicity or the pharmacological activities. Several range of the in vitro methods as well as in vivo studies have been applied throughout the process of clarifying the metabolism of the drug compound.

Direct metabolite quantification in biological samples have been held as one of the most appropriate approaches. However, other approaches such as indirect drug quantification through metabolite hydrolysis or its quantification helps in determining the availability of authentic standards.

Forensic toxicology has been labelled as an advanced scientific analytical technique involving the applications of several hyphenated chromatographic and liquid separation techniques for determining the presence of the toxicants such as harmful substances or metals or pollutants or pesticides.

The toxicokinetic strategy that needs to be opted for determining the alternative route of administration should be determined on the basis of the pharmacokinetic properties of the substance under analysis. The primary objective of this strategy is describing the systemic exposure of the pharmaceutical compound administered in the species under bioanalysis. It is therefore a pre-requisite that the toxicokinetic studies should be well incorporated into the study design. This primarily consists of profiling or monitoring of the systemic drug exposure at appropriate dosing ranges throughout the first repeat dose studies. Subsequently, monitoring as well as profiling of the pharmaceutical compounds may either be extended or reduced or modified for particular compounds where the problems associated have changed the course of the previous toxicity studies.

Toxicokinetics thus, has become an integral part of the non-clinical evaluation programme for enhancing the value of the toxicokinetic data that has been generated in the due course. Such data helps both in understanding the toxicity and comparing it with the relevant clinical data for assessing the risks and safety profiling in humans.  Most critical objectives associated with the investigational procedures of both the toxicological and pharmaceutical drugs is their extraction from their biological matrices. For the past three decades, the analytical instrumentation industry has witnessed a lot of advancements. SPE or liquid-liquid extraction methods have been widely employed in the processes related to the extraction of the active ingredient, its purification and subsequent enrichment.

Toxicological studies represent the entire frame of the analytical process through which the presence or absence of the toxic substance is determined within an analysed sample. This includes estimation of the physicochemical methods for isolating, identifying, and quantifying the presence of toxic substance across different environmental components. ADME/PK analysis usually is employed in the determining both the absorption as well as metabolism. This analysis has become an integral part of the drug research process as any inadequacy detected either in the metabolism or the pk assessment results in NCE failure.

Fortunately, the current efforts invested throughout the drug discovery and development process have re-directed their focus on the process of identification of metabolism and pharmacokinetic issues at the earliest possible stage. This helps in reducing the attrition value of potent drug candidates throughout the developmental stage. A drug’s metabolic fate can be held responsible for problems associated with the factors related to bioavailability, drug-drug interactions, toxicity or the pharmacological activities. Several range of the in vitro methods as well as in vivo studies have been applied throughout the process of clarifying the metabolism of the drug compound.

Direct metabolite quantification in biological samples have been held as one of the most appropriate approaches. However, other approaches such as indirect drug quantification through metabolite hydrolysis or its quantification helps in determining the availability of authentic standards.

Forensic toxicology has been labelled as an advanced scientific analytical technique involving the applications of several hyphenated chromatographic and liquid separation techniques for determining the presence of the toxicants such as harmful substances or metals or pollutants or pesticides.

The toxicokinetic strategy that needs to be opted for determining the alternative route of administration should be determined on the basis of the pharmacokinetic properties of the substance under analysis. The primary objective of this strategy is describing the systemic exposure of the pharmaceutical compound administered in the species under bioanalysis. It is therefore a pre-requisite that the toxicokinetic studies should be well incorporated into the study design. This primarily consists of profiling or monitoring of the systemic drug exposure at appropriate dosing ranges throughout the first repeat dose studies. Subsequently, monitoring as well as profiling of the pharmaceutical compounds may either be extended or reduced or modified for particular compounds where the problems associated have changed the course of the previous toxicity studies.

Toxicokinetics thus, has become an integral part of the non-clinical evaluation programme for enhancing the value of the toxicokinetic data that has been generated in the due course. Such data helps both in understanding the toxicity and comparing it with the relevant clinical data for assessing the risks and safety profiling in humans.