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Clinical Chemistry, Vol 26, 854-860, Copyright © 1980 by American Association for Clinical Chemistry
A Cohen, HS Hertz, J Mandel, RC Paule, R Schaffer, LT Sniegoski, T Sun, MJ Welch and E White 5th
We describe a highly accurate and precise method for determination of total cholesterol in serum by isotope dilution/mass spectrometry. The method was developed for a Study Group of the Committee on Standards of the American Association for Clinical Chemistry, for use in establishing the accuracy of a candidate reference method for total cholesterol, and fulfills their criteria for a definitive method. Cholesterol-d7 is added to serum, with the weight ratio of cholesterol- d7 to total serum cholesterol kept near to 1:1. The esters are hydrolyzed and the cholesterol is separated and converted into the trimethylsilyl ether derivative for measurement by combined gas chromatography/mass spectrometry. The intensity ratio of the molecular ions at m/z 465 and 458 is measured for each sample and for two calibration mixtures, according to a prescribed bracketing protocol. A weight ratio for the sample is obtained by linear interpolation of the ion-intensity ratios, and the total cholesterol is then calculated. The method was applied four times over several weeks to each of five serum pools. Statistical analysis involving consideration of both replication error and variability between weeks gave a coefficient of variation for a single measurement of 0.36%. The absence of interferences in the method was demonstrated by measurements at several other masses.
The following articles in journals at HighWire Press have cited this article:
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  N. G. Dodder, S. S.-C. Tai, L. T. Sniegoski, N. F. Zhang, and M. J. Welch Certification of Creatinine in a Human Serum Reference Material by GC-MS and LC-MS Clin. Chem., September 1, 2007; 53(9): 1694 - 1699. [Abstract] [Full Text] [PDF]
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N. Rifai, G. R. Cooper, W. V. Brown, W. Friedewald, R. J. Havel, G. L. Myers, and G. R. Warnick Clinical Chemistry Journal Has Contributed to Progress in Lipid and Lipoprotein Testing for Fifty Years Clin. Chem., October 1, 2004; 50(10): 1861 - 1870. [Full Text] [PDF]
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G. L. Myers, M. M. Kimberly, P. P. Waymack, S. J. Smith, G. R. Cooper, and E. J. Sampson A Reference Method Laboratory Network for Cholesterol: A Model for Standardization and Improvement of Clinical Laboratory Measurements Clin. Chem., November 1, 2000; 46(11): 1762 - 1772. [Abstract] [Full Text] [PDF]
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D. H. Chace, B. W. Adam, S. J. Smith, J. R. Alexander, S. L. Hillman, and W. H. Hannon Validation of Accuracy-based Amino Acid Reference Materials in Dried-Blood Spots by Tandem Mass Spectrometry for Newborn Screening Assays Clin. Chem., August 1, 1999; 45(8): 1269 - 1277. [Abstract] [Full Text] [PDF]
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R. Kock, B. Delvoux, and H. Greiling Determination of total cholesterol in serum by liquid chromatography–isotope dilution mass spectrometry Clin. Chem., October 1, 1997; 43(10): 1896 - 1903. [Abstract] [Full Text] [PDF]
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J. R. McNamara, E. T. Leary, F. Ceriotti, C. M. Boersma-Cobbaert, T. G. Cole, D. J. Hassemer, M. Nakamura, C. J. Packard, D. W. Seccombe, M. M. Kimberly, et al. Point Status of lipid and lipoprotein standardization Clin. Chem., August 1, 1997; 43(8): 1306 - 1310. [Abstract] [Full Text] [PDF]
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U. Hannestad and A. Lundblad Accurate and precise isotope dilution mass spectrometry method for determining glucose in whole blood Clin. Chem., May 1, 1997; 43(5): 794 - 800. [Abstract] [Full Text] [PDF]
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 J. J. Burke II and P. M. Fischer A Clinician's Guide to the Office Measurement of Cholesterol JAMA, June 17, 1988; 259(23): 3444 - 3448. [Abstract] [PDF]
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