Analytica Chimica Acta 413 (2000) 229–239 Designing experiments to optimise and validate the adsorptive stripping voltammetric determination of nimesulide S. Furlanetto a,∗ , S. Orlandini a , G. Aldini b , R. Gotti c , E. Dreassi d , S. Pinzauti a a Dipartimento di Scienze Farmaceutiche, University of Florence, Via G. Capponi 9, 50121 Firenze, Italy b Istituto Chimico Farmaceutico Tossicologico, University of Milan, Viale Abruzzi 42, 20131 Milano, Italy c Dipartimento di Scienze Farmaceutiche, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy d Dipartimento Farmaco Chimico Tecnologico, University of Siena, Banchi di Sotto 55, 53100 Siena, Italy Received 28 July 1999; received in revised form 29 November 1999; accepted 11 January 2000 Abstract The development and validation, by experimental design, of an adsorptive stripping voltammetric procedure for nimesulide determination is described. A Plackett–Burman matrix and a Doehlert design were used for the screening step and response surface study, respectively. Response surface evaluation allowed the method to be defined robust and robustness testing was considered unnecessary. A full factorial design was employed for intermediate precision determination according to ICH guidelines. Applying the optimised conditions, the linear range was 3.32×10 −9 –3.85×10 −7 M and the dosage form mean recovery was 101.3% with RSD of 1.3% (n=9). ©2000 Elsevier Science B.V. All rights reserved. Keywords: Nimesulide determination; Adsorptive stripping voltammetry; Experimental design; Validation; Dosage form 1. Introduction Nimesulide [4-nitro-2-(phenoxy)methanesulfonani- lide] is a sulfonanilide nonsteroidal anti-inflammatory drug whose anti-inflammatory efficacy has been widely demonstrated and whose analgesic and an- tipyretic activities have also been verified in a broad range of clinical situations [1]. Nimesulide’s pKa value of 6.5 is very important for gastric tolerabil- ity, as it avoids the back diffusion of hydrogen ions responsible for tissue damage [2]. Determination of nimesulide in raw material and in pharmaceutical dosage forms has been carried out by high-performance liquid chromatography [3–6], ∗ Corresponding author. Tel.: +39-055-27-57-305; fax: +39-055-24-07-76. E-mail address: smr@farmfi.scifarm.unifi.it (S. Furlanetto) spectrophotometry [7,8] and differential pulse po- larography [9]. A thin-layer chromatographic method was used for the determination of nimesulide in plasma [10], while the simultaneous determination of nimesulide and its major metabolite hydroxynime- sulide [4-nitro-2-(4 ′ -hydroxyphenoxy) methanesulfo- nanilide] in human plasma and urine was performed by means of a HPLC method [11,12]. Nimesulide is an electroactive molecule which ex- hibits surface properties. The present paper describes the development and validation of an adsorptive strip- ping voltammetric (AdSV) procedure for nimesulide determination in which a pre-concentration step allows low quantitation and detection limits to be obtained. The method can be set up without sample prepara- tion due to the low limits obtained. In fact the sam- ples were highly diluted minimising excipient inter- ference at the electrode surface. The AdSV procedure, 0003-2670/00/$ – see front matter ©2000 Elsevier Science B.V. All rights reserved. PII:S0003-2670(00)00735-2