HPLC Method Development and Optimization with Validation in Mind - Analytical Validation - page 59

• Calibration plots are linear over several orders of magnitude, beginning
with the quantitation limit.
• Suitable accuracy is obtained (perhaps performed in conjunction with
linearity).
• Method- or procedure-appropriate precision is obtained (again, perhaps
performed in conjunction with linearity).
• Demonstration of peak homogeneity (e.g., no co-elutions, or a demonstra-
tion that the method is stability indicating).
System optimization is one of the most time- and energy-consuming parts of the
overall method development procedure. It requires an iterative procedure, constant
replication, and the acquisition of a large amount of quantitative data. Too often, opti-
mization results in a method that meets the immediate requirements of the analyst but
ignores possible future needs. Ideally, the analyst should optimize each new method
to the fullest practical extent in the time available, in order to ensure a broad utility of
the method and obviate the repetition of experiments for future method development.
3.6 summAry
Methods can be developed from scratch through scouting approaches, or adapted
from existing methods found in the literature or other sources. But one thing is
certain: method development is a complex, time-consuming process. Any effort to
streamline, automate, and methodically and logically approach the process can pay
great dividends in terms of throughput, efficiency, and reducing time to market, as
well as producing a method that is easily validated.
reFerences
1. Development and Validation of Analytical Methods , C. M. Riley and T. W. Rosanske,
Editors, Pergamon Press, Elsevier Science, Amsterdam, Holland, 1996.
2. Pharmaceutical and Biomedical Applications of Liquid Chromatography , C. M. Riley,
W. J. Lough, and I. W. Wainer, Editors, Pergamon Press, Elsevier Science, Amsterdam,
Holland, 1994.
3. Snyder, L. R., Glajch, J. L., and Kirkland, J. J., Practical HPLC Method Development ,
John Wiley & Sons, New York, 1988.
4. Snyder, L. R., Glajch, J. L., and Kirkland, J. J., Practical HPLC Method Development ,
2nd edition, Wiley-Interscience, New York, 1997.
5. Neue, U., HPLC Columns, Theory, Technology, and Practice , Wiley-VCH Publishers,
New York, 1997.
6. Snyder, L. R., Kirkland, J. J., and Dolan, J. W., Introduction to Modern Liquid
Chromatography , 3rd edition, John Wiley & Sons, Hoboken, NJ, 2010.
7. Swartz, M. E., Chapter 6: Contemporary liquid chromatographic systems for method
development, pp. 145-186, in HPLC Method Development for Pharmaceuticals , Ahuja,
S., Editor, Elsevier, Burlington, MA, 2007.
8. Dolan, J. W., Snyder, L. R., Djordjevic, N. M., Hill, D. W., Saunders, D. L. Van
Heukelemn, L., and Waeghe, T. J. Simultaneous variation of temperature and gradient
steepness for reversed-phase high-performance liquid chromatography method develop-
ment. I. Application to 14 different samples using computer simulation. J. Chromatogr.,
A , 803, 1, 1998.