Metabolites reference intervals

Reference intervals for plasma and urinary catecholamines and catecholamine metabolites also differ according to sex and age. Females have lower plasma concentrations of epinephrine and metanephrine than males. Similarly, 24-hour urinary outputs of catecholamines and metanephrines are lower in women than men for epinephrine this difference remains significant when values are normalized for creatinine excretion Plasma levels of norepinephrine and normetanephrine increase with advancing age in adults, whereas plasma levels of epinephrine and metanephrine are little affected. Age-related increases in 24-hour urinary outputs of norepinephrine and normetanephrine have also been reported,but not consistently by all studies. In general, the influences of age... 

Premel-Cabic A, Turcant A, AUain P. Normal reference intervals for free catecholamines and their add metabolites in 24-h urines from children, as determined by liquid chromatography with amperometric detection. Clin Chem 1986 32 1585-7. 

A guidance reference interval for plasma PLP is 5 to 30 ng/mL (20 to ninmol/L). " Plasma levels less than 5 ng/mL (20nmol/L) are judged deficient. Guidance values for other vitamin Bg metabolites have been published elsewhere. ... 

Typical reference interval values for whole blood biotin by a microbiological method are 0.5 to 2.20nmol/L, mean 1.31nmol/L. Deficiency is considered likely below 0.5 nmol/L. Reference values for other metabolites and fluids have been published elsewhere. ... 

Figure 55-2 Multi-analyte approach to the prenatal diagnosis of methylmalonic acidemia (cb/C complementation group) by metabolite analysis in ceil-free supernatant of amniotic fluid collected at 16 weeks of gestational age. The symbol marks internal standards. A, Determination of total homocysteine by LC-MS/MS (selected reaction monitoring, SRM, transition m/z 136 to m/z 90 and m/z 140 to m/z 94 for the d -labeled internal standard). The concentration of total homocysteine was l5.7pmol/L (0.7 to 2.0pmol/L). B, Determination of methylmalonic acid by LC-MS/MS (SRM, transition m/z 231 to m/z 119 and m/z 234 to m/z 122 for the d3-labeled internal standard). The concentration of methylmalonic acid was 8.7pmol/L, the reference interval for 16 to 19 weeks of gestational age is 0.2 to 0.7)j,mol/L. C, Determination of propionylcarnitine by LC-MS/MS (parent of m/z 85 scan, the [M+H] ion of C3 is m/z 274, m/z 277 for the interna standard). The concentration was 5.6pmol/L (i.5 to l.8pmoi/L),the C3/C4 ratio was 6.9 (0.9 to 2.6).

Determination ofplasma, urine, or tissue concentrations ofvitamins and their metabolites. These methods depend on comparison of an individual or group with the population reference range, which is normally taken as the 95% confidence interval twice the standard deviation about the mean value. By definition, 5% of the normal healthy population win lie outside the 95% reference range. 

Exposure This term refers to the systemic exposure to drug-related material. It can be expressed as the plasma AUC of administered drug or metabolite within a dosage interval, typically assessed at steady state. The FDA metabolite safety draft guidance also uses the percent of the dose as the measurement of exposure to a metabolite. 

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