Analytica Chimica Acta 405 (2000) 221–226 Tungsten determination in rat and dog plasma samples by inductively coupled plasma emission spectrometry Application to preclinical pharmacokinetic studies Patrick Poucheret a , Sophie Le Lamer a,c , Gérard Cros a , Renaud Kiesgen de Richter b , Pierre-Antoine Bonnet b , Françoise Bressolle c,∗ a Laboratoire de Pharmacologie, Faculté de Pharmacie, Montpellier Cedex 2, France b Agence Française de Sécurité Sanitaire des Produits de Santé, Vendargues, France c Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie, Montpellier Cedex 2, France Received 16 June 1999; received in revised form 24 September 1999; accepted 27 September 1999 Abstract This paper describes an inductively coupled plasma emission spectrometric method for the analysis of tungsten in dog and rat plasma. Calibration curves were obtained in the range 134–1300 ng/ml. The relative standard deviation ranged from 0.4 to 17%, and accuracy was between 89 and 105%. Dilution has no influence on the performance of the method which could then be used to quantitate plasma samples containing up to 90 g/ml. The limit of quantification was 100 ng/ml, at this level, the average relative standard deviation was 17%. The results obtained indicate that the method described for assaying tungsten in plasma samples fulfills the accuracy and precision requirements necessary to carry out pharmacokinetic studies. This method was used to determine pharmacokinetic parameters in rats and dogs. ©2000 Elsevier Science B.V. All rights reserved. Keywords: Inductively coupled plasma atomic emission spectrometry; Tungsten; Biological fluids 1. Introduction Recently, tungstate was found to correct hy- perglycaemia in animal models of diabetes when administered in drinking fluid. More specifically, in insulin-deficient (streptozotocin-induced) rats, normalization of glycaemia was associated with increased glucokinase, 6-phosphofructo-2-kinase and pyruvate kinase activity and decreased phos- ∗ Corresponding author. Tel.: +33-4-67-54-80-75; fax: +33-4- 67-79-32-92 (R)/+33-4-67-54-80-75 (O). E-mail address: FBressolle@aol.com (F. Bressolle). phoenolpyruvate carboxykinase expression to lev- els close to those of healthy animals [1]. In a non-insulin-dependent model of diabetes (the neona- tally streptozotocin-administered rat), it was able to restore the Langherans islet function. Tungstate there- fore, represents a potential treatment of diabetes and should be tested clinically. However, nothing is known at the present time of the tungsten pharmacokinetic behavior, either in animals or in humans. Today, few methods are available to quantify tung- sten in biological samples. Two inductively coupled plasma-mass spectrometry (ICP-MS) methods have been published to quantify tungsten in biological 0003-2670/00/$ – see front matter ©2000 Elsevier Science B.V. All rights reserved. PII:S0003-2670(99)00752-7