Selected Ion Monitoring Gas Chromatography-mass Research Articles

68] Quantitation of the major urinary metabolite of PGF2α in the Human by GC-MS

Publisher Summary The major urinary metabolite of PGF 1α and PGF 2α in man is 5α,7α-dihydroxy-11-ketotetranorprostane- l, 16-dioic acid (PGF-M). PGF-M is the ideal urinary metabolite to monitor in order to detect changes in biosynthesis of the primary prostaglandins as a group. This chapter discusses the quantitation of the major urinary metabolite of PGF 2α in the human. PGF-M exists as an equilibrium mixture of the dioic acid and the corresponding δ-lactone form. The equilibrium is pH dependent. Quantitative conversion to the δ-lactone form is found to occur after 5 min treatment of the open chain acid at pH 1 and after 1 hr at pH 2, while the rate of lactonization is undetectable at pH 5 over the course of 2 hr at room temperature. The assay described in this chapter is based on stable isotope dilution with quantitative analysis by selected ion monitoring gas chromatography–mass spectrometry. It is important to recognize that the objective in a quantitative analysis of PGF-M is measurement of the total amount of free acid plus δ-1actone in the sample; the proportions present as the free acid or δ-1actone are irrelevant, because this is merely dependent on sample pH.

Isotope dilution analysis of methylcitric acid in amniotic fluid for the prenatal diagnosis of propionic and methylmalonic acidemia

A stable isotope dilution assay for methylcitric acid in amniotic fluid was developed to provide rapid prenatal diagnosis of the inherited disorders propionic acidemia and methylmalonic acidemia. The method utilizes two 2H 3-labeled diastereoisomers of methylcitric acid as internal standards, isolation by liquid partition chromatography and quantitation of the trimethyl esters by chemical ionization selected ion monitoring gas chromatography-mass spectrometry. Methylcitric acid at a concentration of 0.38 ± 0.10 μmol/1 was detected in normal amniotic fluid. Highly elevated levels of 7.87 and 9.16 μmol were found in the fluids surrounding fetuses affected with propionic acidemia and levels of 1.79, 2.72 and 12.27 μmol were found for fetuses with methylmalonic acidemia. Methylcitric acid was not elevated in the amniotic fluid of a fetus heterozygous for propionic acidemia. In the five pregnancies at risk for propionic acidemia, and three pregnancies at risk for methylmalonic acidemia, the levels of methylcitric acid in amniotic fluid gave the diagnosis in all cases. Measurement of methylcitric acid in amniotic fluid therefore provides a rapid and reliable method for the prenatal diagnosis of these genetic disorders.

Stereoselective excretion of (3-methoxy-4-sulphooxyphenyl)ethylene glycol (MHPG sulphate) in the dog.

3-Methoxy-4-hydroxyphenylethylene glycol (MHPG) labelled with six deuterium atoms ([2H6]MHPG) was infused into two female greyhound dogs. Plasma and urine were analyzed for endogenous MHPG and [2H6]MHPG and their conjugates by the technique of selected ion monitoring gas chromatography-mass spectrometry. This analysis showed that the major forms of MHPG and [2H6]MHPG in the plasma and urine of the greyhounds were the sulphate conjugates. However, the plasma concentration of [2H6]MHPG sulphate increased continuously during the infusion period and the renal clearance of this compound was found to be much less than that of the endogenous sulphate. The explanation that his was due either to saturation of a renal transport mechanism or to a deuterium isotope effect was eliminated. Stereochemical analysis showed that, while the [2H6]MHPG used for infusion was a racemic mixture of two stereoisomers, much more of the nature(-)stereoisomer of [2H6]MHPG sulphate was excreted in the dog urine. It was also shown that both the (+) and (-)stereoisomers of [2H6]MHPG sulphate were sulphoconjugated at the 4-position of the aromatic ring.

A sensitive method for detection and estimation of juvenile hormones from biological samples by glass capillary combined gas chromatography-selected ion monitoring mass spectrometry

Addition of n-1H,1H,2H,2H-perfluorohexanol (NFH-OH) to the epoxide ring of juvenile hormone (JH)-I, -II, -III, and ethyl-10,11-epoxyfarnesoate (JH-III-Et) yields a stable 10-hydroxy-11-NFH derivative, the mass spectrum of which contains an NFH fragment as base peak. Combination of capillary column gas chromatography-selected ion monitoring mass spectrometry makes it possible to detect and to quantify all the naturally occurring juvenile hormones from biological probes in the femtomole range. Besides high selectivity and sensitivity the method as described works faster than other procedures as extensive purification of the samples is unnecessary. By use of JH-III-Et as internal standard, interference with hormone signals in the selected ion current profile can be avoided and all the homologous juvenile hormones measured simultaneously.

Quantitative analysis of 5-fluorouracil in human serum by selected ion monitoring gas chromatography—mass spectrometry

Quantitative analysis of 5-fluorouracil in human serum by selected ion monitoring gas chromatography—mass spectrometry

A non-enzymic procedure for the quantitative analysis of (3-methoxy-4-sulphoxyphenyl)ethylene glycol (MHPG sulphate) in human urine using stable isotope dilution and gas chromatography—mass spectrometry

A method is described for the quantitative analysis of (3-methoxy-4-sulphoxyphenyl)-ethylene glycol (MHPG sulphate) in human urine, based on selected ion monitoring gas chromatography--mass spectrometry and using a specifically deuterium-labelled analogue of MHPG sulphate as internal standard. The procedure involves extraction of the urine sample on Amberlite XAD-2, followed by isolation of MHPG sulphate by column chromatography on Sephadex LH-20. Cleavage of the sulphate conjugate and formation of the MHPG tris(trifluoroacetate) derivative are carried out in a one-step reaction, without recourse to enzymic hydrolysis.

Free and total 3-methoxy-4-hydroxyphenylethylene glycol in human cerebrospinal fluid: Relationship to blood pressure in hypertensives and patients with neuropsychiatric disease

The concentrations of free and total 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in the cerebrospinal fluid of 43 patients were measured by selected ion monitoring gas chromatography-mass spectrometry using MHPG specifically labelled with deuterium as internal standard. Unpaired Wilcoxon comparisons of free and total MHPG concentrations in males and females showed no significant difference between the sexes. The relationships between free, conjugated and total MHPG concentrations and age, blood pressure, glucose and protein levels in cerebrospinal fluid were examined by linear regression analysis. The only significant correlations found were between free MHPG and glucose and between total MHPG and glucose.