Validation of an alternative two-strip method for the quality control of [99mTc]Tc-ETIFENIN (TECHIDA®)

Abstract

For hepatobiliary scintigraphy, the radiopharmaceutical drug, ETIFENIN (TECHIDA®), labelled with technetium-99m, is used as a substitute for MEBROFENIN (CHOLEDIAM®). It is generally accepted that radiopharmaceuticals should be checked prior to injection, in particular by determining radiochemical purity, to ensure high-quality images. Radiochromatographic techniques or methods described in the Summary of Product Characteristics (SmPC) and the European Pharmacopeia (Ph. Eur.) for quality control of [^99mTc]Tc-ETIFENIN were considered impractical in routine nuclear medicine services (e.g. time-consuming and difficult to use). Following a literature review and screening phase, a quality control method was selected using a two-strip method. For detection and quantification of [^99mTc]TcO₄^-, a glass microfiber paper impregnated with silica acid (ITLC-SA®) was used with a NaCl 20% mobile phase (w/v). For [^99mTc]TcO₂, glass microfiber paper impregnated with silica gel (ITLC-SG®) was used together with an absolute methanol mobile phase. The aim of this work was to validate this alternative analytical method. To do so, the recommendations of the European Association of Nuclear Medicine (EANM), adapted from the International Council of Harmonization Q2 (ICH Q2), were followed. Seven parameters were analyzed: specificity, linearity, precision, accuracy, robustness, limit of quantification and range. Additionally, migration time was also evaluated. This two-strip method appears to be specific (Rs_mean > 2.0), linear (slope close to 1, R² ≥ 0.99), precise (CV < 2.0%), accurate (%impurities_{two-strip method} > %impurities_reference), robust (CV < 2.0%), with an acceptable LoQ (S/N > 10:1) and a wide range (1.6-540 MBq/mL). Time of analysis appears to be clearly integrable into routine clinical practices (< 20 min). The alternative two-strip method NaCl 20% - ITLC-SA® and Methanol - ITLC-SG® represents an efficient quality control procedure. It allows the identification and quantification of the ratios of labelled [^99mTc]Tc-ETIFENIN together with two potential impurities consisting of [^99mTc]TcO₄^- and [^99mTc]TcO₂.

Keywords: Quality control; Radiochemical purity; Validation of method; r-TLC.