Validation of a UV-spectrophotometric analytical method for determination of LPSF/AC04 from inclusion complex and liposomes

Rafaela Siqueira Ferraz,Ivan Rocha Pitta,Suely Lins Galdino,Nereide Stela Santos-Magalhães,Elisângela Afonso Moura Mendonça,Jéssica Priscila Avelino Silva,Maria Do Carmo Alves Lima,Isabella Macário Ferro Cavalcanti,Mariane Cajubá Britto Lira-Nogueira

doi:10.1590/s1984-82502015000100018

Abstract

The aim of this study was to develop and validate a UV spectrophotometric method for determination of LPSF/AC04 from inclusion complex and encapsulated into liposomes. The validation parameters were determined according to the International Conference on Harmonisation (ICH) and National Health Surveillance Agency (ANVISA) guidelines. LPSF/AC04 was determined at 250 nm in methanol by a UV spectrophotometric method, exhibiting linearity in the range from 0.3 to 2 µg.mL−1 (Absorbance=0.18068 x [LPSF/AC04 µg.mL-1] + 0.00348), (r2=0.9995). The limits of detection and quantification were 0.047µg.mL−1 and 0.143µg.mL−1, respectively. The method was accurate, precise, reproducible and robust since all the samples analyzed had coefficient of variation of less than 5% and no statistically significant difference between theoretical and practical concentrations was detected. Thus, a rapid, simple, low cost and sensitive spectrophotometric method was developed and validated for determining the content of inclusion complex and liposomes containing LPSF/AC04.

Highlights

LPSF/AC04 (5Z)-[5-acridine-9-yl-methylene-3(4-methyl-benzyl)-thiazolidine-2,4-dione] (Figure 1A) is an acridinylidene thiazolidinedione, a monoacridinine structural analogue of amsacrine (Figure 1B) (Denny, 2002; Mourão et al, 2005)
A variety of different acridine derivatives has been synthesized and promising results obtained in some cases, prompting the development of new acridine-based drugs that present a wide spectrum of biological activities, such as antibacterial, antimalarial, antitrypanosomial (Bonse et al, 1999), antileishmanial and antiviral (Goodell et al, 2006) actions, and most notably antitumor activity (Goodell et al, 2008)
LPSF/AC04 has shown antitumor activity with tumor inhibition of more than 85% in a murine sarcoma 180 model after 8 days of treatment with 100 mg/kg i.p/day (De Lima, Lins, Pitta, 2007)

Summary

Introduction

LPSF/AC04 (5Z)-[5-acridine-9-yl-methylene-3(4-methyl-benzyl)-thiazolidine-2,4-dione] (Figure 1A) is an acridinylidene thiazolidinedione, a monoacridinine structural analogue of amsacrine (Figure 1B) (Denny, 2002; Mourão et al, 2005). A variety of different acridine derivatives has been synthesized and promising results obtained in some cases, prompting the development of new acridine-based drugs that present a wide spectrum of biological activities, such as antibacterial, antimalarial, antitrypanosomial (Bonse et al, 1999), antileishmanial and antiviral (Goodell et al, 2006) actions, and most notably antitumor activity (Goodell et al, 2008).

Objectives

Methods

Results