Spectrophotometric determination of some antidepressant drugs using 3-methylbenzothiazolin-2-one hydrazone

doi:10.1016/S0928-0987(99)00056-1

European Journal of Pharmaceutical Sciences

Volume 9, Issue 2, December 1999, Pages 221-225

https://doi.org/10.1016/S0928-0987(99)00056-1 Get rights and content

Abstract

A sensitive spectrophotometric method for the determination of amitriptyline hydrochloride, nortriptyline hydrochloride and doxepin hydrochloride in pure and dosage forms, is described. The method is based on the oxidative coupling of the drugs with 3-methylbenzothiazolin-2-one hydrazone in the presence of iron(III) chloride in 1 M hydrochloric acid. The commonly encountered excipients and additives do not interfere with the determinations. Results of the present method are comparable with those of official methods. The new method offers the advantage of simplicity and rapidity.

Introduction

The utility of 3-methylbenzothiazolin-2-one hydrazone (MBTH) was first introduced as a reagent in analytical chemistry for the detection and determination of aldehydes, compounds containing active methylene groups, indoles, aromatic amines, imino-hetero aromatic compounds, arylalkylamines, aryldialkyl amines, carbazoles and phenothiazine type compounds (Sawicki et al., 1961a, Sawicki et al., 1961b). The determination of total aliphatic aldehydes in auto exhaust by a modified MBTH method has been described (Nebel, 1981). The MBTH reagent has been employed for the colorimetric microdetermination of phenols by oxidative coupling method (Friestad et al., 1969). Recently, many workers have been used the MBTH as a spectrophotometric reagent for the determination of some organic compounds containing phenolic moieties (Sastry and Rao, 1989).

Amitriptyline hydrochloride (ATH), nortriptyline hydrochloride (NTH) and doxepin hydrochloride (DOX) are extensively used in the treatment of emotional and psychiatric disorders in which the major symptom is depression, particularly endogeneous depression. Analytical methods for the determination of these drugs include ultra-violet spectrophotometry (Przyborowski and Misztal, 1987), polarography (Chodkowski et al., 1992), spectrophotometry (Abdel Salam et al., 1985, Dembinski, 1992, Mahgoub et al., 1991, Revanasiddappa and Ramappa, 1995, Shingbal and Rao, 1985), potentiometry (Elnemma et al., 1993), gas chromatography (Cyr et al., 1992) and high-performance liquid chromatography (El-Yazigi and Raines, 1993, Haertter and Hiemke, 1992, Haginaka et al., 1990). The official methods of British Pharmacopoeia (1993) and United States Pharmacopoeia (1985) include non-aqueous titration and an ultraviolet spectrophotometric method for dosage forms. The aim of the present work is to provide a simple and rapid spectrophotometric method for the assay of antidepressant drugs in bulk and pharmaceutical formulations, employing MBTH as a chromogenic reagent.

Section snippets

Apparatus

Jasco model UVIDEC-610 and Elico model CL-27 spectrophotometers were used for absorbance measurements.

Standard solutions

Stock solutions of ATH, NTH (Sun Pharmaceutical Industries, Mumbai) and DOX (Intas Laboratories, Ahmedabad, India) were prepared by dissolving the requisite amount of the sample in doubly distilled water.

Results and discussion

The method involves the reaction of DOX, ATH or NTH with MBTH in the presence of an oxidant iron(III) chloride to give blue products with maximum absorption at 620–630 nm. Under reaction conditions, MBTH(I), on oxidation with Fe³⁺ ions, loses two electrons and one proton forming an electrophilic intermediate (II), which is the active coupling species (Bartsch et al., 1970). The electron density in these drugs studied is highest at the two and eight positions, which permits electrophilic

Conclusion

Previously reported methods (Abdel Salam et al., 1985, Revanasiddappa and Ramappa, 1995) for the determination of the antidepressant drugs were less sensitive, time consuming and needed extraction, compared to proposed method. The proposed method which is simple and rapid, offers the advantages of sensitivity and a wide range of determination without the need for extraction or heating. The assay method does not involve any critical reaction conditions or tedious sample preparation. The

Acknowledgements

The authors are thankful to the Quality Control Managers of Sun Pharmaceuticals Ltd. and Intas Laboratories Ltd., India for the supply of pure drug samples. One of the authors (B.M.) is grateful to the University of Mysore, Mysore for providing necessary facilities.

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In addition, extractive fluorimetric methods based on the fluorescent ion pair complex formation of the drug with eosin Y (Rahman et al., 2009) and tetraiodofluorescein (Devriendt et al., 1973) have also been reported for their assay in pharmaceutical preparations and biological fluids. Spectrophotometric methods have also been developed for quantitation of doxepin hydrochloride involving the reagents such as titanium(IV) thiocyanate and iron(III) thiocyanate (Misiuk, 2005), Reinecke salt (Kurzawa et al., 1999), 3-methyl benzothiazolin-2-one hydrazone (Revanasiddappa and Manju, 1999) and bromophenol blue (Shingbal and Rao, 1985). This work describes a new spectrofluorimetric method for the determination of doxepin hydrochloride in bulk and pharmaceutical preparations.
A simple and sensitive spectrofluorimetric method has been developed for the determination of doxepin hydrochloride in pharmaceutical preparations. It is based on the formation of ion-pair complex between doxepin and alizarin red S at pH 3.09. The ion pair complex was extracted in dichloromethane and the fluorescence intensity was measured at 560 nm after excitation at 490 nm. The optimum conditions for determination were also investigated. The linear range and detection limit were found to be 2–14 and 0.55 μg/ml, respectively. The method has been successfully applied for the analysis of drug in commercial dosage forms. No interference was observed from common pharmaceutical adjuvant. Statistical comparison of the results obtained by the proposed method with that of the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.
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The applicability of the proposed methods for the determination of doxepin in commercial dosage forms was examined by analyzing marketed products. The results of the proposed methods were statistically compared with those obtained by the reference method [28], and the comparative data are summarized in Table 6. It is evident from the table that the calculated t- and F values are less than the theoretical ones at 95% confidence level, indicating no significant difference between the methods compared.
Charge transfer complexes of the doxepin with π – acceptors such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), tetracyanoquinodimethane (TCNQ) and p-chloranilic acid (p-CA) have been studied spectrophotometrically. The stoichiometry of the reactions was studied by Job's method of continuous variations which show that the complexation ratio was 1:1 (acceptor: donor) for DDQ, TCNQ and p-chloranilic acid with doxepin base. The data were discussed in terms of association constant (K), molar absorptivity (ε), free energy change (ΔG), oscillator strength (f), transition dipole moment (μ_EN), resonance energy (R_N) and ionization potential (I_D). Three simple, fast and sensitive spectrophotometric methods were proposed for the quantification of doxepin hydrochloride in pure form and drug formulations. The methods (A, B and C) were based on the reaction of doxepin base as n-donor with DDQ, TCNQ and pCA resulting in coloured species which absorbed maximally at 570 nm, 840 nm and 530 nm, respectively. Beer's law was obeyed in the concentration range of 5–45 μg mL^− 1, 40–360 μg mL^− 1, and 40–400 μg mL^− 1 for the methods A, B, and C, respectively. A series of variables were studied to optimize the reaction conditions. The developed methods were successfully applied for the determination of doxepin in its formulations with high accuracy and precision and without interference from common excipients.
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Acrolein can be at the origin of an important organoleptic defect in beverages made from apples. Its content was investigated in freshly distilled Calvados and cider. The specificity of 3-methylbenzothiazolone hydrazine (MBTH) towards carbonyl compounds was used in order to derive acrolein in azines. Azines were separated and detected by gas chromatography coupled with a nitrogen–phosphorus Detector. Results showed that acrolein concentrations could be quickly determined in either Calvados or cider. Accuracy of quantification was better than 6% for concentrations about 1 mg/l in freshly distilled Calvados and 10% for concentrations about 10 μg/l in ciders. Acrolein content was found between 0.7 and 5.2 mg/l in samples of freshly distilled Calvados whereas it was between 7 and 15 μg/l in samples of cider. This method of quantification was applied to study disappearance kinetics of acrolein in cider. Acrolein content was found to decrease rapidly during the first hours and to change very slowly after a few days. Its behaviour during a distillation was also investigated showing that in spite of its high volatility it could also be found in the last fractions of distillation.
Gas chromatographic quantification of aliphatic aldehydes in freshly distilled Calvados and Cognac using 3-methylbenzothiazolin-2-one hydrazone as derivative agent
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A new precise and sensitive method was used for the quantification of aliphatic aldehydes from C₅ to C₁₁ in highly ethanolic beverages such as freshly distilled spirits. Carbonyl compounds were derivatized using 3-methylbenzothiazolin-2-one hydrazone (MBTH) and then separated and detected by gas chromatography–mass spectrometry (GC–MS). Selective mass spectrometric detection of molecular ions of derivatives was performed to obtain a good sensibility (0.2–1.2 μg l⁻¹) and a good selectivity. For a concentration of 20 μg l⁻¹, relative standard deviations were lower than 10% except for heaviest compounds (decanal and undecanal) where RSD were between 11 and 13%. The concentrations of aliphatic aldehydes were determined in nine samples of freshly distilled Calvados and two samples of freshly distilled Cognac with highest concentrations reported for 3-methylbutanal (from 170 to 1220 μg l⁻¹ in Calvados and from 1540 to 5500 μg l⁻¹ in Cognac). 3-Methylbutanal and hexanal, due to their low detection thresholds, could be important olfactive markers of these two products. Less than 1h30 is required to quantify the nine studied aliphatic aldehydes in freshly distilled spirits.
Extractive spectrophotometric methods for the determination of doxepin hydrochloride in pharmaceutical preparations using titanium (IV) and iron (III) thiocyanate complexes
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A large number of organic substances, drugs, and excipients interfere significantly. This fact justified the development of different analytical techniques, e.g., polarography and spectrophotometry with colour reagents such as hexaiodobismuthate, KMnO4 in NaOH medium, formaldehyde in H2SO4 medium, 3-methylbenzothiazolin-2-one hydrazone or with bromophenol blue [8–12]. Gas liquid chromatography, high performance liquid chromatography, thin-layer chromatography, and capillary electrophoresis [13–26] have been applied to determination of doxepin in biological fluids.
Two simple, precise, and accurate extractive spectrophotometric methods have been developed for the determination of doxepin hydrochloride in pharmaceutical preparations. The methods are based on the formation of ion association complexes of doxepin with titanium (IV) and iron (III) thiocyanate complexes in acidic medium. The produced compounds are insoluble in water but well soluble in some organic solvents. They are extracted with mixtures of butyl alcohol–chloroform (2:3, v/v) and (1:4, v/v) and measured spectrophotometrically at 400 and 490 nm for DOX–Ti-SCN and DOX–Fe(III)-SCN methods, respectively. Beer’s law was obeyed in the concentration ranges of 5–50 and 3–30 μg/ml with molar absorptivity of 7.12 × 10³ and 1.36∙× 10⁴ l mol^–1 cm^–1 for DOX–Ti-SCN and DOX–Fe-SCN systems, respectively. The proposed methods have been successfully applied for the analysis of the drug in dosage forms. No interference was observed from common pharmaceutical adjuvants. The methods have been also used for the determination of the drug in the presence of its degradation product. Statistical comparison of the obtained results with the reference methods shows excellent agreement and indicates no significant difference in accuracy and precision.
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View full text

Spectrophotometric determination of some antidepressant drugs using 3-methylbenzothiazolin-2-one hydrazone

Abstract

Introduction

Section snippets

Apparatus

Standard solutions

Results and discussion

Conclusion

Acknowledgements

J. Chromatogr.

Spectrophotometric determination of some tranquilizers and antidepressant using 2,3-dichloro-5,6-dicyano-p-benzoquinone

Anal. Lett.

Mechanism of oxidation of 3-methyl-2-benzothiazolinone hydrazone by potassium ferricyanide in aqueous methanol

J. Am. Chem. Soc.

Polarographic determination of doxepin hydrochloride

Chem. Anal. (Warsaw)

Gas-chromatographic methods for doxepin isomers, related compounds and organic volatile impurities in raw materials and doxepin isomers in capsules

J. Assoc. Off. Anal. Chem. Int.

Spectrophotometric determination of doxepin

Chem. Anal. (Warsaw)

Determination of amitriptyline, imipramine and orphenadrine in antidepressant drugs by potentiometry, spectrophotometry and atomic-absorption spectrometry

Mikrochim. Acta

Concurrent liquid-chromatographic measurement of fluoxetine, amitriptyline, imipramine and their active metabolites nor-fluoxetine, nortriptyline and desipramine in plasma

Ther. Drug Monit.

Automated colorimetric microdetermination of phonols by oxidative coupling with 3-methyl-2-benzothiazolinone hydrazone

Anal. Chem.