Direct Determination of ECD in ECD Kit: A Solid Sample Quantitation Method for Active Pharmaceutical Ingredient in Drug Product

Abstract

Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N′-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03–0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method.

Study of Degradation Products and Degradation Pathways of ECD and Its Drug Product, ECD Kit

“…The study of Tsopelas et al (2005) was mainly focused on the behavior of Tc-99m and its reactions with components of ECD Kit. Our preliminary observations showing that ECD Kit is highly unstable in (non)aqueous solution and the composition of ECD Kit is the major obstacle to determine stability of ECD (Chao et al, 2011). Therefore, the aim of this paper is to evaluate degradation kinetics and mechanism of ECD Kit in aqueous solution.…”