Determination of the coumarin anticoagulant phenprocoumon and metabolites in human plasma, urine and breast milk by high-performance liquid chromatography after solid-phase extraction.

The coumarin anticoagulant phenprocoumon (PH) and metabolites (6-, 7- and 4'-hydroxyphenprocoumon) were analysed in plasma and urine samples from anticoagulated patients using solid-phase extraction and high-performance liquid chromatography with reversed-phase columns and ultraviolet and fluorescence detection; a simpler handling of samples, higher selectivity, precision, accuracy and analytical recovery were obtained compared to analysis using liquid-liquid extraction. Similarly, a method for the analysis of PH in human breast milk was developed to assess the passage of anticoagulants into breast milk in anticoagulated lactating women.

[Transfer of phenprocoumon in breast milk. Is oral anticoagulation with phenprocoumon a contraindication for breastfeeding?]. / Transfer von Phenprocoumon in die Muttermilch. Ist eine orale Antikoagulation mit Phenprocoumon eine Kontraindikation für das Stillen?

UNLABELLED: As the passage of phenprocoumon into human milk has not been studied yet, mothers on oral anticoagulation with Phenprocoumon are advised to stop breastfeeding in order to avoid the potential hazards of vitamin K deficiency haemorrhage in their babies. We analysed the passage of Phenprocoumon into human milk in a breastfeeding mother of a premature baby (gestational age 32 weeks), who required oral anticoagulation on day 19 post partum. The mother was advised to continue collecting her milk with an electric pump, and to resume breastfeeding, if a significant passage of the drug was excluded. Milk Sampling (fore and hind milk pairs (n = 2), for milk (n = 4), 24 h pooled collections) for the Phenprocoumon analyses with an HPLC method was performed on days 27, 28, and 31 when the Quick's Prothrombin time was stable in the therapeutic range (Phenprocoumon plasma concentrations: 1.8-2.2 micrograms/ml). RESULTS: Phenprocoumon was higher in hind than in foremilk. With constant plasma concentrations the variability between different foremilk samples was 26-76 ng/ml. The Phenprocoumon concentration in the 24 h pooled sample was 33 ng/ml. Estimates of the Phenprocoumon secretion into human breast milk should be from pooled milk samples of a 24 h collection. Phenprocoumon in human milk is only about 1/50 of the corresponding maternal plasma concentrations. The estimated daily Phenprocoumon intake from maternal milk in a baby drinking about 200 ml/kg/day is 6-8 micrograms/kg. This is much less the average maintenance requirement for anticoagulation with Phenprocoumon in children (about 50 micrograms/kg/day).(ABSTRACT TRUNCATED AT 250 WORDS)