The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health (NIH), has developed a Standard Reference Material (SRM) to support technology development in metabolomics research. SRM 1950 Metabolites in Human Plasma is intended to have metabolite concentrations that are representative of those found in adult human plasma. The plasma used in the preparation of SRM 1950 was collected from both male and female donors, and donor ethnicity targets were selected based upon the ethnic makeup of the U.S. population. Metabolomics research is diverse in terms of both instrumentation and scientific goals. This SRM was designed to apply broadly to the field, not toward specific applications. Therefore, concentrations of approximately 100 analytes, including amino acids, fatty acids, trace elements, vitamins, hormones, selenoproteins, clinical markers, and perfluorinated compounds (PFCs), were determined. Value assignment measurements were performed by NIST and the Centers for Disease Control and Prevention (CDC). SRM 1950 is the first reference material developed specifically for metabolomics research.

Methods for extraction of cocaine, some of its metabolites, morphine, and codeine from hair and methods for analyzing the extracts have been investigated. Results of these studies have shown that extractions with 0.1N HCl are efficient at removing the target compounds from hair and appear to be as effective as enzymatic digestions that dissolve the hair. GC/MS with either electron ionization or chemical ionization was found to provide accurate and unambiguous determinations of the target compounds. Tandem mass spectrometry (MS/MS) also provided accurate results when performed on extracts from hair, but results were ambiguous when MS/MS was performed on hair segments directly. Environmental issues, including the removal of powdered and vapor-deposited cocaine from the hair surface and the effect of various hair treatments on the levels of cocaine entrapped in hair, have also been investigated. Removal of cocaine deposited on hair was incomplete by all approaches tested, making differentiation of hair of cocaine users from hair with environmental exposure of cocaine difficult. Cocaethylene, a cocaine metabolite believed to be formed in the liver, was found in the hair of some cocaine users and may be a good marker for proving drug use. Common hair treatments, such as shampoos, conditioners, and peroxide bleaches, reduced cocaine levels in a fortified hair material by 60 to 80% after 30 treatments. Finally, to assist laboratories in evaluating the accuracy of their methods, two human hair reference materials with recommended concentrations of cocaine, benzoylecgonine, morphine, and codeine determined by GC/MS have been developed.

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.

An Isotope dilution mass spectrometrlc (ID/MS) method for serum creatinine Is described which uses creatlnlne-13C2 as the labeled Internal standard. Creatinine Is separated from creatine and converted to the ethyl ester of A/-(4,6-dlmethyl-2-pyrlmldlnyl)-IV-methylglyclne. Combined capillary column gas chromatography and electron Impact mass spectrometry are used to obtain the abundance ratio of the unlabeled and labeled [M -COOC2Hs]+ Ions from the derivative. Quantitation Is achieved by measurement of each sample between measurements of two standards whose unlabeled/labeled ratios bracket that of the sample. Four freeze-dried human serum pools Including National Bureau of Standards Standard Reference Material 909 were analyzed with this method. The coefficients of variation for a single measurement ranged from 0.15 to 0.27% for the four pools. The measurements were found to be free of Interference. The high precision and absence of significant bias qualify this method as a candidate definitive method.Serum creatinine concentrations are commonly measured in clinical laboratories in evaluating renal function. Clinical methods generally involve a version of the Jaffe method or an enzymatic procedure (1). Because of significant discrepancies in results among the methods in use (2), a need exists for a method of demonstrated accuracy and precision, i.e., a definitive method, to provide an accuracy base against which the other methods can be judged. Universal acceptance of