ABSTRACT
The efficiency of 1D and 2D NMR spectroscopy along with HPLC-DAD-MS analyses in characterising the content of a dietary supplement is demonstrated. Experiments directly performed on a lyophilised sample of a commercial product gave details on the quality control of the product. The lack of the marker constituents of some of the declared plant species (Crataegus oxyacantha, Olea europea, Capsella bursa-pastoris and Fumaria officinalis) and the presence of banned adulterants, responsible for the strong antihypertensive effect of the supplement were established. The analyses proved the presence of indole alkaloids belonging to the group of Rauwolfia sp., such as ajmaline, reserpine and yohimbine. Quantitative HPLC analysis showed that the content of reserpine in the product was in the therapeutic range and therefore responsible for the collapses of the patients.
Subject(s)
Antihypertensive Agents/adverse effects , Dietary Supplements/analysis , Drug Contamination , Plant Extracts/analysis , Alkaloids/analysis , Antihypertensive Agents/analysis , Calibration , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Pharmacovigilance , Plant Leaves , Plants, Medicinal , Quality Control , Rauwolfia/metabolism , Technology, PharmaceuticalABSTRACT
OBJECTIVE: While propranolol pharmacokinetics has been extensively studied in adults, this study reports the first evaluation of propranolol pharmacokinetics in term and preterm neonates. METHODS: Propranolol concentrations were measured in four term and 32 preterm newborns treated with oral propranolol at the dose of 0.5 or 0.25 mg/kg every 6 h by serial dried blood spots. RESULTS: The levels of propranolol, although with high inter-individual variability, were proportional with the administered dose. Pharmacokinetic parameters evaluated at the steady state in newborns treated with 0.5 mg/kg/6 h showed values of maximal (71.7 ± 29.8 ng/mL), minimal (42.2 ± 20.8 ng/mL) and average concentration (60.8 ± 25.0 ng/mL), time of maximal concentration (2.6 ± 0.9 h) and area under the time-concentration curve (364.7 ± 150.2 ng/mL/h) similar to those observed in adults. In both dosing groups, elimination half-life was significantly longer (14.9 ± 4.3 and 15.9 ± 6.1 h), and apparent total body clearance (27.2 ± 13.9 and 31.3 ± 13.3 mL/kg/min) lower than those reported in adults, suggesting a slower metabolism in newborns. No differences were observed between newborns with different gestational age or different sex. CONCLUSIONS: Neonates treated with propranolol-exhibited drug concentrations proportional with the dose, with significant long half-life.
