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Author(s): Taranjeet Kukreja, Swarnlata Saraf

Email(s): swarnlatasaraf@gmail.com

Address: University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur - 492010, Chhattisgarh, India.
University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur - 492010, Chhattisgarh, India.
*Corresponding Author: swarnlatasaraf@gmail.com

Published In:   Volume - 35,      Issue - 2,     Year - 2022


Cite this article:
Kukreja and Saraf (2022). UV Spectroscopy Analysis for Itraconazole . Journal of Ravishankar University (Part-B: Science), 35(2), pp. 62-67.



UV Spectroscopy Analysis for Itraconazole

Taranjeet Kukreja1, Swarnlata Saraf *

1University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur - 492010, Chhattisgarh, India

*Corresponding Author: swarnlatasaraf@gmail.com

Abstract:

Itraconazole is a triazole antifungal agent that is synthesised. Itraconazole has been manufactured into a variety of pharmacological formulations and administered in a variety of ways. Itraconazole pills are used to treat pulmonary fungi that can cause fungal infection and spread throughout the body. Because Itraconazole is not yet officially listed in any pharmacopoeia, only a few procedures for quality control and stability testing in pharmaceutical formulations have been published. The goal of this study is to develop a more precise, easy, and cost-effective spectrophotometric approach for analysing Itraconazole in bulk and capsule dosage forms with improved precision, accuracy, and sensitivity. The UV spectroscopic determination was performed with Chloroform as the solvent at an absorption maximum of 267 nm. Linearity over the concentration range in the UV spectroscopic approach. The linearity of Itraconazole over the concentration range was found to be 1-10 g/ml using the UV spectroscopic technique, with a correlation coefficient of 0.999. The findings of the analyses were statistically and the recovery studies have confirmed this.

Keywords: Itraconazole, pharmacopoeia, UV spectroscopic technique, Quality control.

 

Introduction

Itraconazole is a triazole antifungal agent that is synthesised. Itraconazole is a racemic combination of four diastereomers (two enantiomeric pairs), each with three chiral centres, in a ratio of 1:1:1:1. The following nomenclature can be used to denote it: 4-[4-[4-[4-[[ 2. (2, 4-dichlorophenyl) - two (1H-1, 2, 4- triazole- 1-ylmethyl) - 1,3- dioxolan-4-yl] methoxy]phenyl] piperazine-1- yl]phenyl] piperazine-1- yl]phenyl] piperazine-1- yl]phenyl] piperazine-1- yl]phenyl] piperazine-1- -2-(1-methyl propyl) -2, 4-dihydro-1, 2-dihydro-1, 2-dihydro-1, 2-dihydro-1, 2-dihydro-1, 2-dihydro (Fig 1).

Figure1: Itraconazole's structure

C35H38Cl2N8O4 is the molecular formula and the chemical molecular weight is noted to be705.64. [1-4] It's a powder that's white to slightly yellowish. In alcohols, it is very partially soluble, but in dichloromethane, it is completely soluble. Itraconazole is an extremely lipophilic compound that is water insoluble. It's a very weak base (pKa =3.7) that only ionises at very low pH levels. It's a three-chiral hydrophobic antimycotic medication that's employed in clinical trials as a stereoisomeric combination. [5] It is an oral triazole antifungal medication efficacious against dermatophytes, species of bacteria, Malassezia, and penicillium species having a broad range of activity and Histoplasma capsulatum var. capsulatum, among other fungal species. [6,7]

 

Mechanism of action of Itraconazole

It binds to 14-demethylase, a cytochrome P-450 enzyme that is required for the conversion of lanosterol to ergosterol. Because ergosterol is a necessary component of the fungal cell membrane, inhibiting its synthesis increases cellular permeability, causing cellular contents to flow out. Itraconazole can also decrease endogenous respiration, interact with membrane phospholipids, prevent yeasts from transforming into mycelial forms, block purine uptake, and disrupt triglyceride and/or phospholipid production. When itraconazole is taken with food, its oral bioavailability increases and plasma concentrations are nearly twice as high as when taken when fasting. Itraconazole is metabolised primarily in the liver by the cytochrome p450 3a4 isoenzyme system, which produces various metabolites, the most significant of which is hydroxyl itraconazole 8. [9] It is metabolised in the liver, primarily through an oxidative pathway, forming the bioactive metabolite hydroxyl itraconazole. [10]

 

Materials and methods

Experimental

Chemicals and reagents: Throughout UV spectrophotometric technique, development and validation Chloroform was used.

 

Instrumentation

UV spectrophotometric technique was performed on a double beam UV-visible spectrophotometer (Shimadzu, model 1800) having two matched quartz cells with a 1 cm light path.

 

Selection of solvent

For the analysis of Itraconazole, Chloroform had been selected as the ideal solvent for spectrophotometry.

 

Standard stock solutions preparation

A 10 mg Itraconazole reference standard was accurately weighed and transferred to a 10 ml volumetric flask, where it was dissolved and diluted up to the mark using chloroform to yield a stock solution with a strength of 500g/ml. Diluting 1 ml of stock solution to 5 ml with chloroform yielded a 50 g/ml working standard solution.

Preparation of Sample stock solution

For analysis of the drug, 10mg of the drug itraconazole was weighed and transferred to a 10ml volumetric flask and dissolved with chloroform. The itraconazole drug solution was diluted to get a final concentration of 10μg/ml. The absorbance of these solutions was measured at 267 nm. The amount of Itraconazole was calculated using the calibration curve.

 

Formula:

 %Purity=Sample absorbance / Standard absorbance X 100

1.     Method validation

The method was validated according to the International Conference on Harmonization (ICH)

Q2B guidelines 1996 for validation of analytical procedure to determine the linearity,

limit of detection, accuracy and precision.

 

2.     Linearity & Range

Under the experimental conditions, the calibration graphs of the absorbance versus

Concentration was found to be linear over the range of 0.2-1.0μg/ml for the proposed method.

The statistical analysis of data obtained for estimation of Itraconazole is indicated chloroform

of accuracy for the proposed methods evidenced by the low values of standard deviation and

coefficient of variation. The results are noted below:

Table 1: Itraconazole Linearity Data

S. No.

Concentration in μg/ml

Absorbance in UV

1

0

0

2

2

0.1316

3

4

0.2520

4

6

0.3527

5

8

0.4713

6

10

0.5813

 

y = 0.0575x + 0.0106

slope = 0.057

RSQ = 0.9986

 

 

Results and Discussion

The purpose of this study was to validate an Itraconazole using a UV-Spectrophotometric technique under optimal conditions. The validation parameters' results were found to be within acceptable limits. Within the concentration range of 1-10g/ml, itraconazole followed linearity. The measured linearity range suited Beer-law Lambert's well, and the corresponding regression coefficient (r=0.999) indicates a high degree of technique sensitivity, as shown in Table 1. The number of drugs detected and the findings of the analysis demonstrate that the percentage of the drugs found and the number of drugs found was in good accord.

 

Conclusion

UV-Spectrophotometer techniques produced equivalent results. The linearity of Itraconazole over the concentration range was found to be 1-10 g/ml using the UV spectroscopic technique, with a correlation coefficient of 0.999. The findings of the analyses were statistically and the recovery studies have been confirmed.

 

Acknowledgment

I am thankful to the University Institute of Pharmacy (UIOP), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India for my practical support. I also want to thank Prof. Swarnlata Saraf, University Institute of Pharmacy (UIOP), Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India for her valuable suggestions and guidance.

 

References:

1.     Khoschsorur G, Frueehwirth F, Zelzer S.Isocratic High-Performance Liquid Chromatographic Method with UV detection for simultaneous determination of voriconazole and itraconazole and its hydroxyl metabolite in human serum. Antimicrobial agents and Chemotherapy, 2005; 49: 3569-3571.

2.     Conway SP, Etherington C, Peckham DG et al. Pharmacokinetics and safety of Itraconazole in patients with cystic fibrosis. Journal of Antimicrobial Chemotherapy,2004; 53: 841-847.

3.     European Pharmacopoeia. Itraconazole, Strasbourg: France, 4thEd, 2005; 1852-1853.

4.     Hay R.J, Dupont B, Graybill J.R. Review Infectious Disease, 1987; 9(Suppl. 1): S1-3

5.     Saag M.S, Dismukes W.E. Antimicrobial Agents Chemotherapy, 1988.

6.      Mechanism of action available online at URL http://www.drugbank.ca/drugs/DB01167.

7.     De Beule K, Van Gestel J. Pharmacology of Itraconazole, 2001; 61(S1): 27–37.

8.      Pharmaceutical applications are available online at URLhttp://www.nlm.nih.gov.

9.      Shalin K. Parikh, Ankit D. Patel, Dr J. B. Dave, Dr C. N. Patel and Dr D. J. Sen, “Development and validation of UV Spectrophotometric method for estimation of itraconazole bulk drug and pharmaceutical formulation” International Journal of Drug Development and Research, 2011; 3(2): 324-328.Stefanie Redmann, Bruce G. Charles, “A rapid HPLC method with fluorometric detection for the determination of plasma itraconazole and hydroxy-itraconazole concentrations in cystic fibrosis children with allergic bronchopulmonary aspergillosis” BiomedicalChromatography, 2006; 20(4): 343–348.

10.  Kramer M, Marshall S, Denning D et al. Cyclosporine and Itraconazole Interaction in Heart and Lung Transplant Recipients. Annals of Internal Medicine, 1990; 113: 327–329.

11.  D. Vijaya Bharathi, Kishore Kumar Hotha, P.V.Vidya Sagar, Sanagapati Sirish Kumar, Pandu Ranga Reddy, A. Naidu, Ramesh Mullangi, “Development and validation of a highly sensitive and robust LC-MS/MS with electrospray ionization method for simultaneous quantitation of itraconazole and hydroxyitraconazole in human plasma” Science Direct Journal, 2008; 868(1-2): 70-76.

12.  Ming Yao, Laishun Chen, Nuggehally R Srinivas, “Quantitation of itraconazole in rat heparinized plasma by liquid chromatography-mass spectrometry” Journal of Chromatography B: Biomedical Sciences and Applications, 2001; 752(1)5: March 2001;916.

13.  Srivatsan V, Dasgupta A, Kale P, Datla R, Soni D, Patel M, Patel R, and Mavadhiya, C. Simultaneous determination of itraconazole and hydroxyitraconazole in human plasma by high-performance liquid chromatography, Journal of Chromatography, 2004; 1031: 307-313.

14.  Zimmermann T, Yeates R.A, Laufen H. European Journal of Clinical Pharmacology, 1994; 46: 147.

15.  Constantinos Kousoulos, Georgia Tsatsou, Constantinos Apostolou, Yannis Dotsikas and Yannis L. Loukas, “Development of a high-throughput method for the determination of itraconazole and its hydroxy metabolite in human plasma, employing automated liquid-liquid extraction based on 96-well format plates and LC/MS/MS ” Analytical and Bioanalytical Chemistry, 2006; 384(1): 199-207.

16.  M. V. Kumudhavalli, “Isocratic RP-HPLC, UV Method Development and Validation Of Itraconazole In Capsule Dosage Form” International Journal of Pharmaceutical Research IJPSR, 2011; 2(12): 3269-3271.

17.   Al-Rawithi H, Sameer M, Hussein A, Rajaa Al-Moshen, Ibrahim, Raines, Dale, et al. Determination of Itraconazole and Hydroxy itraconazole in Plasma by High-Performance Liquid Chromatography with Fluorescence Detection, Therapeutic Drug Monitoring, 2001; 23: 445-448.

18.  El-Enany N, El-Sherbilny D, Belal F. Spectrofluorimetric Determination of Itraconazole in Dosage Forms and Spiked Human Plasma. Journal of the Chinese Chemical Society, 2007; 54: 375-382.



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