Microcoated wire sensors for the determination of anticancer drugs cyclophosphamide and ifosphamide in the presence of their degradates

The construction and electrochemical response characteristics of poly (vinyl chloride) and poly (vinyl chloride) carboxylate membrane sensors for the determination of cyclophosphamide and ifosphamide are described. Based on the formation of an ion-pair complex between the drug cation and sodium tetraphenylborate, two poly (vinyl chloride) sensors, namely a cyclophosphamide membrane sensor and ifosphamide membrane sensor were fabricated. They show a linear response for both drugs over the concentration range 10⁻²–10⁻⁴ M with cationic slopes of 56 and 54.6 mV per concentration decade, for sensor 1 and sensor 2, respectively. Based on the interaction between the drug solution and the dissociated COOH groups in the poly (vinyl chloride) carboxylate, sensor 3 was fabricated. It shows a linear response for both drugs over the concentration range 10⁻³–10⁻⁵ M with a cationic slope of 49.7 mV per concentration decade. The direct potentiometric determination of cyclophosphamide and ifosphamide in their pharmaceutical preparations using the proposed sensors gave average recoveries of 101.3±0.6, 100.8±10.7 and 102.0±11.0% for the sensors 1, 2 and 3, respectively, which compares reasonably well with the data obtained using the British Pharmacopoeial method (1993). Sensors 1 and 2 were also used to follow up the stability of the drugs studied in the presence of their degradates. These degradation products have no diverse effect on the responses of sensors 1 and 2.     

Spectrophotometric and Spectrofluorimetric Determination of Cyclophosphamide and Its Isomer Ifosphamide

Abstract

Based on the condensation reaction between amino groups of either cyclophosphamide or ifosphamide with the carbonyl group of ninhydrin, giving coloured and fluorescent products, a spectrophotometric procedure for both drugs is suggested in the range from 30 to 90μg ml^?1 at 564 nm, with accuracies of 100.6 ± 1.06% and 100.8 ± 1.02% for cyclophosphamide and ifosphamide, respectively. Also, a spectrophotometric procedure for both drugs is proposed in the range from 1.2 to 3.6 μg ml^?1 at 465 nm and 485 nm for cyclophosphamide and ifosphamide, respectively, using 380 nm as an excitation wavelength for both drugs with accuracies of 100.4 ± 1.83% and 99.5 ± 1.64%, respectively. This condensation reaction, however, does not differentiate between the two isomeric drugs.

Another new method is, therefore, suggested. It depends on the fact that the secondary amino group of ifosphamide is hindered electronically and sterically, while the nucleophilic amino group of cyclophosphamide reacts with the nitrosyl group of sodium nitroprusside molecule, giving a bluish green colour measurable at 708 nm. This colour is used for the determination of cyclophospahmide in the presence of its isomer ifophamide in the range from 0.2 to 1 mg ml^?1 with repeatability of 99.2 ± 1.49%.

The suggested procedures are applied successfully to pharmaceutical formulations of cyclophosphamide and ifosphamide, and their validities are assessed by applying the standard addition technique. The results obtained by applying the proposed procedures are statistically analyzed and compared with those obtained by adopting the United States Pharmacopoeial method.