Quantitative gas chromatographic determination of two oxidized metabolites of the diuretic mefruside in human urine, plasma and red blood cells.

A gas chromatographic method is reported for the quantitative analysis of two metabolites of mefruside, viz., 5-oxo-mefruside (mefruside lactone) and its hydroxy-carboxylic acid analogue in human body fluids. Use was made of extractive methylation as the derivatization technique, and quantitation was achieved, with a suitable internal standard, by means of a nitrogen-sensitive detector. Because the two metabolites are linked chemically through a lactone-open acid equilibrium, interconversion prior to their separation had to be avoided. A pH partitioning study was performed to find optimal separation conditions. The lactone could be extracted quantitatively at pH 7.4, without any trace of co-extracted hydroxy acid. The latter was extracted either at pH 2 directly (in the case of plasma and urine), or after conversion to the lactone at pH 7.4 (in the case of red cells or whole blood). Concentrations down to 25 ng per sample of both compounds could be analysed with a standard deviation of 5%. The two metabolites of mefruside equilibrated instantaneously between red cells and plasma in vitro. At 37 degrees, the red cell/plasma concentration ratio was 20 for the lactone, but only 0.1 for the open acid compound. 5-Oxo-mefruside was able to displace mefruside from its red blood cell binding sites in vitro.

[Hyperreninism without hyperaldosteronism in diuretic abuse: a report of a case with identification of mefruside and ethacrynic acid in urine (author's transl)]. / Hyperreninismus ohne Aldosteronismus bei Diuretika-Abusus. Kasuistik mit Nachweis von Ethacrynsäure und Mefrusid im Harn.

A 46-year-old nurse had been hospitalized 16 times during the preceding five years because of episodes of excessive hypokalaemia. On admission to hospital there was hypokalaemia, polyuria, excessive plasma renin activity but no increased aldosterone secretion rate. Diuretic abuse was confirmed by gas-chromatography and mass spectrometry of mefruside and ethacrynic acid in the patient's urine. Apart from other interesting aspects of this case there was the demonstration of hyperreninism without hyperaldo-steronism. The stimulating effect of renin on aldosterone secretion was obviously lower than the inhibiting effect of hypokalaemia. The general term "renin-angiotensin-aldosterone system" is, therefore, misleading because it mentions only one pathway of aldosterone regulation. The combination of hypokalaemia, polyuria, hyperreninism without hyperaldosteronism is apparently the principal but not widely recognised feature of diuretic abuse.