APPLICATION OF AN EXPANDED MODEL PROCEDURE FOR TRANSFER OF TLC SCREENING METHODS FOR SUBSTANDARD AND FAKE DRUGS DESIGNED FOR USE IN DEVELOPING COUNTRIES TO QUANTITATIVE HPTLC-DENSITOMETRY METHODS

Abstract

Transfer of four rapid thin-layer chromatography (TLC) screening methods used to detect substandard and fake pharmaceutical products to quantitative high-performance TLC (HPTLC)-densitometry methods is demonstrated using an expanded version of a model procedure that was published earlier. These methods for mebendazole, diphenhydramine hydrochloride, amodiaquine, and artesunate are contained in a Compendium of methods by Kenyon and Layloff and/or Minilab method manuals from Global Pharma Health Fund E.V. for use in countries with limited resources. A new HPTLC-densitometry method was also developed for amitriptyline hydrochloride, for which there was no Compendium or Minilab method that could be transferred. These quantitative methods use Merck HPTLC silica gel 60 F₂₅₄ glass plates, automated standard and sample solution application, and automated densitometry for detection, identification, and quantification. Standard and sample solution preparation and application procedures for obtaining calibration curves and bracketed samples are described. Additions to the previous model procedure include peak identity and purity checks by spectral comparison. HPTLC gives better efficiency, selectivity, and resolution than TLC, and the new methods overcome the deficiencies in technology related to manual application and visual zone comparison that do not allow the Compendium and Minilab TLC procedures to support regulatory compliance actions. These new methods can be fully validated according to International Conference on Harmonization (ICH) guidelines or by interlaboratory studies if their applications require.

Keywords:

• amitriptyline hydrochloride
• amodiaquine
• artesunate
• densitometry
• diphenhydramine hydrochloride
• mebendazole
• thin-layer chromatography

ACKNOWLEDGMENT

The authors thank Thomas Layloff, Senior Quality Assurance Advisor, Supply Chain Management System (SCMS), Arlington, VA, for offering valuable suggestions during the completion of this research; reviewing the manuscript prior to its submission for publication; and arranging for delivery of samples of mebendazole, amitriptyline, and artesunate-amodiaquine pharmaceutical products that are prone to faking and corresponding reference materials needed for method development. Samples were supplied by the Dar es Salaam, Tanzania, office of SCMS, and the reference materials were supplied by the Arlington, VA, USA, office. Kristi Lianza was supported by the Lafayette College EXCEL Scholars Program.