Desenvolvimento de métodos simples e rápidos para determinação de paracetamol e outros fármacos em formulações farmacêuticas por eletroforese capilar com detecção condutométrica sem contato (CE-C4DC4D)

Abstract

The preset work shows new analytical procedures which were developed for fast determination of paracetamol (PAR), in the presence of codeine (COD), orphenadrine (ORP), promethazine (PRO), scopolamine (SCO), tramadol (TRA), ibuprofen (IBU), caffeine (CAF), acetyl salicylic acid (AAS), dipyrone (DIP), pyridoxine (PIR), diclofenac (DCF), ascorbic acid (ASC) and naproxen (NAP), with low times of electrophoretic run, below 2 minutes, without pre-treatment of the samples or several dilutions, by capillary electrophoresis with contactless capacitivity coupled condutometric detection (CE-C4D). SCO pKa value was obtained experimentally (pKasco≈10.2). Five distinct methods were developed, with five distinct background electrolytes (BGE). For determination of PAR and the organic cationic analytes was used the BGE 1: 10 mmol L-1 β-alanine + 4 mmol L-1 NaCl + NaOH, (pH 9.6), for determination of PAR and the organic anionic analytes, in the presence and also in the abscense of CAF on the drug formulation: for PAR, IBU and CAF was used the BGE 2: 10 mmol L-1 3,4-dimethoxycinamic acid (DMX), 10 mmol L-1 β-alanine + LiOH, pH = 10.4), for PAR and NAP; BGE 3: 20 mmol L-1 β alanine + KOH, (pH = 10.5); and for PAR, DIP and AAS; PAR, PIR and ASC; and PAR with DCF, the BGE 1 was used. When CAF was presents in the formulation, BGE 4: 10 mmol L-1 DMX + 20 mmol L-1 β-alanine + NaOH (pH = 10.4) was used instead of BGE 1. The strategy of use NaCl in the BGE composition was proposed to elevate the conductivity, thus, showing a better signal to noise ratio (SNR), improving the sensitivity for the analytes. The proposed methods shown low relative standard deviation for peak area (< 2.2 %) and for migration time (< 0.9 %). In addition, good resolutions (> 1.34) between the analytical signal from each species. Good linearity correlation were obtained (> 0.989); and accuracy procedures with commercial formulations has shown recovery of 91% to 104%. The limits of detections (LOD) were between 0.6 e 48.7 μmol L-1; and despite these values can be considerably high, they are more than suitable for pharmaceutical analysis. The proposed methods are also fast (≈29 injections per hour), with low toxicity reagents consumption (≈ 3 mL of BGE per day of work) and, therefore, low residues generation, being considerate a green method and agreeing with the analytical and environmental chemistry trends.