Page 1203 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1134 SECTION | XVII Analytical Toxicology

VetBooks.ir METHOD DEVELOPMENT IN VETERINARY and that there is frequent communication between the lab-
oratory and the client as development proceeds. Even the
ANALYTICAL TOXICOLOGY
most experienced toxicologist or chemist can’t foresee all
It is not uncommon for laboratories to get requests for
analyses for which they have no analytical method in of the possible problems that may arise during the devel-
opment of a new method.
place. Depending on the nature of the situation (the num-
ber of animals involved, the potential for a problem in the
human food supply, etc.), the laboratory may need to Analytical Standards
develop a new method. These development projects may
be fairly simple, involving the addition of a new analyte Most analytical methods rely on the comparison between
into an existing method or replicating a method from the the analysis of a sample and the analysis of a chemical
scientific literature. These projects may also be quite com- standard. One of the first questions that must be resolved
plex, involving multiple trials to optimize the extraction prior to method development is whether a chemical stan-
and analysis conditions and even collaborative method val- dard is commercially available. The standard usually con-
idation among multiple laboratories. Good communication sists of the pure analyte, purchased from a supply house
between the laboratory and their client is essential for the that provides documentation of the identity and purity of
laboratory personnel to understand the client’s needs and the compound. The standard is analyzed to determine
for the client to understand the process the laboratory will method parameters, such as the chromatographic retention
have to follow to meet those needs. Issues involving costs, time or mass spectrum, and to document that the instru-
turnaround times, detection limit requirements, and quanti- ment is functioning properly for the analysis. For quanti-
tative precision should be determined prior to the initiation tative methods, a standard is used to determine the
of the development process. Laboratory personnel must response of the detector to a specific amount of the chem-
make an honest determination of their ability to meet the ical in order to measure the concentration in a sample.
client’s needs and of the resources, which will be required Standards are also “spiked” into control samples prior to
for the successful development of the method. analysis in order to provide quality control (QC) informa-
Some questions to consider prior to the start of a tion. The availability of pure analytical standards is criti-
method development project: cal to the performance of most testing in a toxicology lab.
Another type of standard is known as a “standard ref-
What are the analytes and the sample types?
erence material” or SRM. An SRM consists of a sample
What amount of sample is available? Is there enough
such as feed or tissue in which the analyte is known to be
that the lab will be able to provide relevant results?
present. The SRM is analyzed by a number of different
How much time is available for method development?
labs in order to establish a reference concentration of the
How many samples will ultimately be analyzed using
analyte. Labs may then purchase the reference material
the new method?
and analyze it in order to demonstrate the accuracy of the
Will there be specific turnaround time requirements
analytical process. SRMs are mostly used in elemental
for sample analysis once the method is in place?
analysis, as they are rarely available for the types of
What are the required detection limits?
organic tests performed in veterinary toxicology.
Will the method need to provide quantitative data or
strictly qualitative (detected/not detected) results
What is the end-use of the data? Will it be used for
regulatory actions, legal proceedings, research, or Selectivity
other uses?
Selectivity describes the ability of a technique to reliably
Are there other specific data quality requirements?
differentiate an analyte from the many other chemical
(For instance, does the lab need to follow FDA
components in a sample. A technique with a high degree
method validation guidelines?)
of selectivity will be less prone to false positive detections
What is the cost estimate for the development
than a technique with a lower degree of selectivity. A
process?
high degree of selectivity in a method gives a high degree
Once the method is in place, what is the cost estimate
of confidence in the identification of analytes. A method
for sample analysis?
with a relatively low level of selectivity may require a
The development process will establish several aspects second confirmatory test in order to confidently report a
of the method. These include availability of analytical result. Method development generally involves analysis
standards, selectivity, sensitivity, and the detection/quanti- of samples known to be free of the analyte in order to
tation/reporting limits. It’s important that needs and ensure that the method can discriminate the analyte from
expectations for these method parameters are established other constituents in the matrix.