315 zyxwvuts JournaZ of Chromatognzphy, 145 (1978) 315-318 Biomedical Applications o Elsevier zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Scientific Publishing Company, Amsterdam - Printed in The Netherlands . . CHROMBIti. 102 Note Simple and sensitive method for the deter&&ion of cyclophosphamide by means of a nitrogr?n-phasphorus-selective detector TRRRNZIO FACCHINEXTI, $QUJRUXO ti’INCALC1, GIAMPIERO MARTELLI, LAVI- NIA CANTONI, GIORGIO BELVEDERE and MARIO SALMONA Zstituto di Ricerche FarmacotogHze ‘Wario Negrif’, Via Eritrea 62. 20157 M&m (Ztaty) (First received March 29th, 1977; revised manuscript received July 4th, 1977) Cyclophosphamide (Cy) (Fig. -1) is widely used as an anti-tumoral agent in various clinical protocols [I]. The need for information on the bioavailability of this compound makes it important to have at our dispo+ sensitive analyt- ical methods for measuring Cy plasma levels. Pantarotto et al. [2] have pub- lished a Gas Chromatographic (GC) method based on derivatization of the drug with trifluoroactive anhydride. Although this method satisfies the need for high sensitivity, apart from derivatization problems, it also calls for an expensive electron capture detector. Cl-CH,- CH, $?,“-CH2 ;N-P, 'kH, Cl-CH,-CH, NH-CH,' Fig. 1; Structure of cyclophosphamide. In this paper we present a GC method using a nitrogen-phosphorus-selec- tive detector (NPSD) which can detect aa little as 10 ng/ml of the compound without any derivatization. It is possible to measure plasma levels of patients treated with a single intravenous dose of 100 mg of Cy. MATERIALS AND METHODS Uzenzictzls Cyclo~hosptiamide,as the.,hydrate sak, was kindly donhzd by the Chest&r Beatty Institute (London, Great Britain). Imipramine,.used as internal stan-