SULM – Schweizerische Union für Labormedizin | Union Suisse de Médecine de Laboratoire | Swiss Union of Laboratory Medicine

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KM Rentsch1 , U Gutteck1 , A von Eckardstein1

1Institute for Clinical Chemistry, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland

Objective: Due to their metabolism by cytochrome P450 enzymes (mainly CYP3A4) the lipid lowering statin drugs have become interesting for pharmacokinetic interaction studies. In order to perform these investigations, sensitive and specific analytical techniques are needed to quantify these drugs in blood samples. The analytical method for the quantification of simvastatin (1) was adapted for the determination of pravastatin.

Methods: Simvastatin and its metabolite beta-hydroxy acid as well as pravastatin and its metabolite pravastatin lactone have been extracted from serum samples by liquid-liquid cartridge extraction. The internal standards used were lovastatin and triamcinolone for the simvastatin and pravastatin assays, respectively. Separation of the different compounds have been performed by reversed-phase HPLC with a mixture of acetonitrile and ammonium acetate buffer (pH 4) as the mobile phase. After electrospray ionisation (ESI), tandem mass spectrometry was used as the detection method.

Results: The intra- and interassay inprecision for all analytes was < 10% and the accuracy ranged from 90 to 106 %. The methods were linear in the range of 0.05 to 20 µg/l for simvastatin and its metabolite and 0.1 to 30 µg/l for pravastatin and its metabolite. At acidic pH, pravastatin can isomerise to SQ-31906. This isomerisation process has been investigated and during normal analytical runs no increase of the isomer concentration was determined.

Summary and conclusions: Due to the high precision and accuracy, as well as the high analytical sensitivity, the described methods are very useful for the determination of pravastatin and simvastatin in pharmacokinetic interaction studies.

(1) Zhao JJ, Xie IH, Yang AY, Roadcap BA, Rogers JD. J Mass Spectrom 2000;35:1133-43.

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