We are beginning a discussion of “gold standard” analytical techniques. My definition of a “gold standard” is any method which accurately and reproducibly determines the concentration of the analyte being measured. A “gold standard method” must accurately quantitate any control prepared in the biological matrix being analyzed. Stated another way, even if an assay is calibrated in an artificial matrix for use in analyzing human serum, it must be able to accurately quantitate the analyte in controls prepared in human serum.
I have marveled at the technological changes which have occurred over the last 50 years. Especially interesting to me (among many), have been those related to analytical techniques utilized to quantitate bio-markers. When I began working in TDM in the 60s, the two most common techniques for measuring anti-epileptic drugs (AED) were ultraviolet spectrophotometry (UV) and a colorimetric procedure known as the “Dill method”. Even, at that time there was a question as to which was the better method to be utilized in routine patient care. Unfortunately, AEDs have very similar structures and therefore there was much cross-reactivity and interference with the techniques regardless of which method you used.
In the late 60s and early 70s, gas liquid chromatography (GLC) was introduced into the Clinical Laboratory. It was by far more specific and accurate method than the earlier UV and colorimetric techniques. Consequently, GLC became the “gold standard” analytical technique for the determination of drugs in biological fluids. High pressure Liquid Chromatography (LC) was introduced in the mid-70s. LC was as accurate as GLC and was easier to use. Both techniques have their limitations and both were prone to interference from various biological constituents present in the patient specimens.
Introduction of LC started another argument about the “gold standard” method for detection of drugs and other compounds in biological fluids. For several years the argument raged back and forth with proponents adamantly arguing for their favorite. The debate was never resolved; although, the ease of LC ultimately resulted in the displacement of GLC except in toxicology laboratories which utilized both techniques.
We have just considered a few historical facts surrounding what determines a “gold standard” analytical technique. We will continue this discussion in the next blog.
About C. E. PIPPENGER, PH.D.
Dr. Pippenger is an Adjunct Professor in the Department of Neurosciences, University of Vermont, College of Medicine, Burlington, Vermont. After receiving his Ph.D. in Pharmacology from Purdue University in 1971, Dr. Pippenger was named Director of the Anticonvulsant Drug Evaluation Laboratory in the Department of Neurology at Columbia University College of Physicians and Surgeons. In 1975, he was promoted to Assistant Professor of Neuropharmacology in Neurology, and, in 1980, to Associate Professor of Neuropharmacology in Neurology at Columbia. In 1979, he was founding editor of the journal Therapeutic Drug Monitoring, and was co-editor until 1990. He also helped establish, with support from the Epilepsy Foundation of America, the Antiepileptic Drug Levels Quality Control Program, which was continued by the American Association for Clinical Chemistry as their Laboratory Improvement Program. From 1982 to 1990, he was on the staff of the Cleveland Clinic Foundation, where he headed the Section of Applied Clinical Pharmacology/Trace Metals in the Department of Biochemistry. He was Vice President of Research and Development, and Laboratory Director, at FRESA BioMedical Laboratories, Inc., from 1991-1995. From 1995 to 2002, Dr. Pippenger was the Director of the Peter C. and Pat Cook Health Sciences Research and Education Institute in Grand Rapids, Michigan. He was the Peter C. and Pat Cook Research Professor in the Department of Biomedical/Health Sciences at Grand Valley State University, Allendale, Michigan from 2002-2004.
Dr. Pippenger’s research interests are in clinical pharmacology and pharmacokinetics, anticonvulsant and convulsant drugs, pediatric and geriatric clinical pharmacology, biochemical pharmacology, trace elements, the role of glycoproteins in cellular communication and disease, and the role of free radicals in neurological disease. His major research efforts are directed to providing better treatment for patients with the epilepsies and free radical mediated diseases. He is the author of more than 150 scientific papers and co-editor of six books. A Fellow of the International League of Epilepsy and a Fellow of the National Academy of Clinical Biochemistry, Dr. Pippenger has received numerous awards including the President’s Award and Outstanding Scientist Awards from the American Association for Clinical Chemistry, the Distinguished Service Award from the Epilepsy Foundation of America, and The William G. Lennox Award granted by the American Epilepsy Society and the William G. Lennox Trust.