Sterol profiling in red blood cell membranes and plasma of newborns receiving total parenteral nutrition.

BACKGROUND AND OBJECTIVES: Total parenteral nutrition (TPN) is a lifesaving therapy in children with intestinal failure, frequently complicated by liver dysfunction. Plant sterols (phytosterols) of lipid emulsions have been supposed to contribute to cholestasis in TPN-treated children. The present study aimed to evaluate the plasma and red blood cell membrane (RBCM) phytosterol levels in newborns after a short period of TPN. PATIENTS AND METHODS: Phytosterols, cholesterol, and other sterol levels were quantified by gas chromatography-mass spectrometry in 15 healthy control infants, 22 patients after TPN, and 11 patients before TPN. Sterols of lipid emulsions were quantified. RESULTS: Plasma and RBCM phytosterol levels were, respectively, on average 56 micromol/L and 83 micromol/g per protein in patients after TPN, 13 micromol/L and 15 micromol/g per protein in patients before TPN, and 9 micromol/L and 13 micromoL/g per protein in control infants (P < 0.05 for differences). The days of TPN and the total amount of infused lipids correlated significantly with RBCM phytosterol (P < 0.05); correlations for plasma were positive but not significant. No correlation was observed with plasma bilirubin, gamma-glutamyltransferase, or alanine transaminase. CONCLUSIONS: Plasma and RBCM phytosterols increase significantly in newborns after a short period of TPN. Higher phytosterol levels were observed in some patients that could have been due to their individual variability in phytosterol metabolism and/or clearance. A greater accumulation of phytosterols in membranes may induce TPN-related cholestasis.

Development and validation of a LC/MS/MS method for simultaneous quantification of oxcarbazepine and its main metabolites in human serum.

A fast, sensitive and specific LC/MS/MS method for the simultaneous analysis of oxcarbazepine (OXC), 10-hydroxycarbazepine (MHD) and trans-diol-carbazepine (DHD), in human serum, has been developed and validated. Serum drugs were extracted by C8 solid-phase cartridges (SPE) and separated in less than 3 min on a C18 reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring. Calibration curves, obtained on two ranges of concentration (0.78-50 mg/L for MHD and 0.078-5.0 mg/L for OXC and DHD), showed correlation coefficients (r) better than 0.997. Within day and between days quality controls imprecision, as CV%, ranged from 0.3 to 4.6% and from 1.9 to 5.8%, respectively. Cyheptamide (CYE) was used as internal standard. No detectable carry-over and no relevant cross-talk and matrix effect occurred. Samples from 24 treated patients were analysed and drug serum concentrations obtained by this method are in agreement with those of other methods and also are well correlated (r=0.88) in comparison to our routine HPLC-UV method. Based on the analytical results and short run time, the method is suitable to support routine analysis of therapeutic drugs monitoring from human serum of treated patients or for pharmacokinetic studies.