The Halogen Bond between Amantadine and Iodine and Its Application in the Determination of Amantadine Hydrochloride in Pharmaceuticals

• Published in: Analytical Sciences 2014/03/10, Vol.30(3), pp.365-370
• Main Authors: YAN, Xiao Qing, WANG, Hui, CHEN, Wei Di, JIN, Wei Jun
• Format: Article
• Language: English
• Subjects: amantadine; Amantadine - chemistry; amantadine hydrochloride; Analytical Chemistry; charge transfer; Chemistry; Halogen bond; iodine; Iodine - chemistry; N+···Nlep bond; Pharmaceutical Preparations - analysis; primary amine cation
• ISSN: 0910-6340; 1348-2246
• DOI: 10.2116/analsci.30.365

It is proposed that molecular iodine as a donor could form halogen bonding complexes with amantadine (AMD) and amantadine hydrochloride (AMD-HCl) in chloroform and the resultant charge transfer bands (CT band) would be located at 259 and 253 nm, respectively. The halogen bonding interaction was explored by UV absorption, Raman and X-ray crystallography, and a new bonding model named N+···Nlep bond in crystal was observed. The halogen bonding complexes were utilized in the development of simple and accurate spectrophotometry for the analysis of AMD/AMD-HCl. Compared with the traditional method based on the absorption of I3− at 290 and 365 nm, the new proposed spectrometry based on the CT band of halogen bonding complex was more sensitive and selective for the detection of AMD/AMD-HCl. Linear relationships with good correlation coefficients (>0.9994) were obtained between the absorbance and the AMD/AMD-HCl concentration in the range of 10 – 180 μg mL−1 for AMD-HCl and 0.2 – 13 μg mL−1 for AMD. The limit of detection (LOD) was 2.23 μg mL−1 and limit of quantification (LOQ) was 7.45 μg mL−1 for AMD-HCl. And because of the stronger bond constant between AMD and iodine than AMD-HCl, the method is more sensitive for AMD; the LOD was 0.02 μg mL−1 and LOQ was 0.08 μg mL−1 which was 100 times lower than that of AMD-HCl.