Modifications in electrospray tandem mass spectrometry for a neonatal-screening pilot study in Japan

Improvements of hypertriglyceridemia and hyperlacticemia in Japanese children with glycogen storage disease type Ia by medium-chain triglyceride milk

“…Serum total carnitine and acylcarnitine levels were determined by an enzymatic cycling method described by Takahashi et al [18]. Acylcarnitine profiles were examined by tandem mass spectrometry according to a method described by Shigematsu et al [16].…”

Dried blood spot sampling in combination with LC‐MS/MS for quantitative analysis of small molecules

“…However, the specifi city of MS/MS assay alone (infusion or fl ow injection) is often hampered by interferences of the matrix components, especially those sharing the same MS/MS transitions with the target analytes. The presence of isomeric and/or isobaric interference components has been reported to contribute to the higher incidences of false-positive results from the measurement of branch-chain amino acids, isovalerylglycine and C 4 /C 5 acylcarnitines that are, respectively, associated with the diagnosis of maple syrup urine disease, isovaleric academia and short-chain acyl-coenzyme A dehydrogenase defi ciency (Abdenur et al, 1998;Chace et al, 1995;Garg and Dasouki, 2006;Oglesbee et al, 2008;Shigematsu et al, 1999 and2007). Furthermore, the possible in-source fragmentation in the case that the target analyte is a derivative of another intact biomarker molecule and natural isotope contribution might add another challenge to MS/MS (infusion or fl ow injection) only assays (Garg and Dasouki, 2006;Piraud et al, 2003).…”

Mass spectrometry in metabolome analysis

“…Another interesting example recently published by Nagy et al (2003) is the method for the analysis of 19 amino acids in dry blood spots. Compared to the well-established method that includes a butyl-esterification of the free carboxyl groups of amino acids to enhance the electrospray ionization efficiency (Rashed et al, 1995;Chace et al, 1996Chace et al, , 1998Shigematsu et al, 1999;Zytkovicz et al, 2001), the new method does not require any derivatization of the amino acids before ESI-MS-MS analysis. That method is, therefore, not limited to the analysis of compounds that have a butyl-formate loss in connection with derivatization.…”

“…Although more amino acids can be characterized by this method, the suitability of the method for quantitative analysis has not been evaluated, and the method involves a derivatization step. Acylcarinitines have also been the target in the screening of newborns because the accumulation of these compounds in blood or urine indicates organic acidaemias and fatty-acid oxidation defects (Rashed et al, 1995(Rashed et al, , 1997Chace et al, 1997;Shigematsu et al, 1999;Vreken et al, 1999;Mueller et al, 2003). Acylcarinitines, as well as amino acids, from dried blood spots were analyzed by ESI-MS after butyl-esterification.…”

“…With the aid of automated sample preparation, and of computers to assist in the recognition of a specific disease in a patient, rapid MS-MS analysis can now be used to perform realtime newborn screening (Rashed et al, 1997;Shigematsu et al, 1999). In the medical area, very high and reproducible sample throughput has been achieved with tandem MS for the analysis of an array of metabolic disorders, and already in 2000, more than 1 million blood and plasma samples had been tested by MS in laboratories throughout the world (Chace, DiPerna, & Naylor, 1999).…”