Spectrophotometric Determination of Rifampicin through Chelate Formation and Charge Transfer Complexation in Pharmaceutical Preparation and Biological Fluids

Abstract

Rifampicin, 3-[[4-methyl-1-piperazinyl)-imino]-methyl]-rifamycin SV, (RIF) (Fig. 1a) is a semi-synthetic derivative of Rifamycin SV.1,2) It can be used alone or in combination with other drugs, such as isoniazid (INH) and pyrazinamide, in treatment of tuberculosis, leprosy and other infectious diseases specially those resulting from AIDS. The high occurrence of tuberculosis in HIV infected subjects makes the management of HIV treatment complex. RIF is a very active antituberculosis drug that accelerates the metabolism of protease inhibitors. 3,4) Due to the increasing necessity to monitor plasma concentrations in HIV patients with tuberculosis, different methods such as spectroscopy, 5-9) fluorometry, [10][11][12] gas chromatography, 13) polarography, 14) amperometry 15) and high performance liquid chromatography [16][17][18][19][20][21] have been developed to measure RIF alone or in the presence of INH. These methods are expensive and need more expertise in experimentation in comparison with spectrophotometry.Spectrohotometric techniques continue to be the most preferred method for routine analytical work due to their simplicity and reasonable sensitivity with significant economical advantages. On the other hand, it is well known that p-benzoquinones such as 7,7,7,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 2,3,5,6-Tetrachloro-1,4-benzoquinone (p-chloranil) as pelectron acceptors (Fig. 1b) often form highly colored electron-donor-acceptor (EDA) or charge transfer (CT) complexes with various donors which provides the possibility of determination of drugs by spectrophotometric methods.In order to develop a new method for determination of RIF in pure and pharmaceutical forms as well as characterize the behavior of RIF in EDA chemistry, we investigated spectrophotometrically the reactions of RIF with organic p-acceptors DDQ, TCNQ and p-chloranil. The absence of an extraction step in these assays and the efficiency of the method offer the ease and rapidity desired for measurement of RIF. Also, an extractive-spectrophotometric method based on the reaction of RIF with iron(III) was developed. The results were compared with other similar methods. The reaction pathways were investigated by IR and 1 H-NMR spectra. Results and DiscussionRIF was found to yield intense colors with p-acceptors in acetonitrile solution, most probably due to the CT complexation of RIF as n-electron donor with DDQ, TCNQ and pchloranil as p-electron acceptors. Figure 2 shows the absorption spectra of RIF, DDQ, TCNQ and p-chloranil and their complexes in acetonitrile. Acetonitrile was found to be an ideal solvent for the formation of charge transfer (CT) complex. Methanol, dichloromethane, chloroform and mixtures of methanol-acetonitrile were examined and produced lower absorbance reading. Acetonitrile was chosen as the best solvent due to intensely colored CT complex with high molar absorptivity values and more reproducibility of the measure- Two simple and accurate spectrophotometric methods for deter...

Structural characterization of molecular complexes formed by trimethoprim and cimitidine with 2,3,5,6-tetrachloro-1,4-benzoquinone

“…The molecular interaction between electron donors and electron acceptors play an essential role in the analysis of drugs in pure dosage forms of pharmaceutical preparation [1,2], solar energy [3], surface chemistry [4], biological fields [5] and in many chemical reactions [6][7][8]. These complexes have also received great attention for non-linear optical materials and electrical conductivities [9][10][11][12].…”

“…This attempt aims to spectroscopically characterize the mechanism of interaction of these drugs with a biologically significant quinone. Various spectroscopic techniques such as UV/vis, FT-IR, 1 H NMR and spectrofluorimetry were employed in the present study. The results obtained in the present study would definitely help to understand the mechanism of interaction of these drugs in real situation and also in the analytical estimation of these drugs.…”

Synthesis and spectroscopic studies of charge transfer complexes between chloranilic acid and some heterocyclic amines in ethanol

“…In through last few decades, charge transfer complexes play an essential role in the analysis of some drugs in pure form or pharmaceutical preparation [1,2], solar energy storage [3] and surface chemistry [4] as well as many biological fields [5], charge transfer complexes are found to take part in many chemical reactions, like addition, substitution and condensation [6][7][8]. These complexes have great attention for non-linear optical materials and electrical conductivities [9][10][11][12].…”

The Synthesis of Novel Mono(alkoxy)-, Tris(thio)- and Tetrakis(thio)-Substituted Quinones from the Reactions of p-Chloranil with Various S-Nucleophiles

“…4,10-14 p-Chloranil and its derivatives behave as electron acceptors in the reaction of charge-tranfer complexes. 4,[15][16][17][18][19][20] Thioethers which are synthesized from the reactions of thiols with quinones are known as thioquinones. 11,13 Tetrakis(thio)-substituted-1,4-benzoquinone compounds are used in the dye industry.…”