A systematic review of hair cortisol during pregnancy: Reference ranges and methodological considerations.

The present study systematically reviewed 56 articles that assessed hair cortisol concentrations during pregnancy collected from PubMed, Scopus, and Web of Science on 8/9/19 and updated on 6/29/20. Our goals were to establish reference ranges by trimester based on published studies. The majority of any given sample (e.g., 70 %, the range of -1SD to +1SD) is expected to fall between 0 and 34.15 pg/mg in trimester 1 and 2, and between 8.59 and 44 pg/mg in trimester 3, with very wide ranges (e.g., values of >250 pg/mg) and substantially higher values (e.g., averages of 200's-300's reaching as high as 768 pg/mg) coming out of one specific lab. Delineating a reference range for hair cortisol concentrations across pregnancy is challenging because of known factors like differences in values returned by different laboratories and assay types. We observed inconsistency in descriptions of the data and data preparation steps post-assay. Key findings include that only half of the studies examining all three trimesters showed a constant increase in mean levels (most retrospectively assessed via segmenting), with considerable variability in patterns of change. None of the studies reported individual patterns of change. Examining within-person changes are an important next step for the field. We conclude that researchers should more clearly report decisions around outliers, units, and specifics of data transformations in the future in order to improve our ability to compare findings across studies, to understand differences in HCC values reported, and potentially to understand differences in reported associations of HCC with other phenotypes in the literature.

UHPLC-MS/MS bioanalysis of urinary DHEA, cortisone and their hydroxylated metabolites as potential biomarkers for CYP3A-mediated drug-drug interactions.

AIM: A UHPLC-MS/MS assay was developed to quantify urinary dehydroepiandrosterone (DHEA), 7ß-hydroxy-DHEA, cortisone and 6ß-hydroxycortisone as potential biomarkers to predict CYP3A activity. RESULTS: A sensitive assay at LLOQ of 0.500 ng/ml with good accuracy and precision was developed for the four analytes in human urine. This UHPLC-MS/MS assay was optimized by eliminating nonspecific loss of the analytes in urine, ensuring complete hydrolysis of the conjugates to unconjugated forms and use of the product ions of [M+H-H2O]+ for multiple reaction monitoring detection of DHEA and 7ß-hydroxy-DHEA. CONCLUSION: This assay was successfully applied to a pilot clinical study. It is also suitable for future drug-drug interaction studies to continue evaluating the potential of these steroids as biomarkers for CYP3A inhibition and induction.

Cortisol and cortisone ratio in urine: LC-MS/MS method validation and preliminary clinical application.

BACKGROUND: The determination of urinary cortisol/cortisone ratio is of clinical utility in cases of Cushing's syndrome, apparent mineralocorticoid excess, and also provides information on 11ß-hydroxysteroid dehydrogenase (11ß-HSD) type 2 activity. It is therefore of utmost importance to ensure accurate cortisol and cortisone measurement and establish appropriate reference ranges. METHODS: After the isotopic dilution of urine, sample cleanups were obtained with on-line solid-phase extraction and cortisol and cortisone, separated using a Zorbax Eclipse XDB-C18 HPLC analytical column, were analyzed by tandem mass spectrometry with an electrospray ionization source in positive ion mode operation. RESULTS: The method was linear, with concentrations of up to 625 and 1125 nmol/L and lower limit of quantitation (LLOQ) of 5 and 6 nmol/L, for cortisol and cortisone, respectively. Within-run and between-run coefficients of variation were <5% and 6% for cortisol and 6% and 8% for cortisone, respectively. No ion suppression was observed. The non-parametric reference range for the cortisol/cortisone ratio was 0.14-1.09. CONCLUSIONS: A simple and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the measurement of cortisol and cortisone in urine. Our findings indicate that the proposed analytical method is suitable for routine purposes and useful in many pathological conditions.

[Cortisone Acetate Reference Standard (Control 921) of National Institute of Health Sciences].

The raw material of cortisone acetate was tested for the preparation of "Cortisone Acetate Reference Standard (Control 921)". The quality of the raw material was examined and compared with the previous Cortisone Acetate Reference Standard (Control 743). Analytical data obtained were as follows: loss on drying, 0.06%; melting point, 245.9 degrees C (decomposition); optical rotation, [alpha]20D = +215.5 degrees; UV spectrum, lambda max = 239 nm and specific absorbance E 1%1 cm (239 nm) = 393; infrared spectrum, the same as that of the previous Reference Standard (Control 743); thin-layer chromatography, no impurities were detected up to 100 micrograms; high-performance liquid chromatography (HPLC), three impurities were detected; assay, 100.5% by HPLC. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 921).