Vol 10, Issue 5, 2017
Online - 2455-3891
Print - 0974-2441
ULTRAVIOLET-HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD DEVELOPMENT
AND VALIDATION FOR QUANTIFICATION OF BESIFLOXACIN HYDROCHLORIDE
BIJIT SAHA
1
*, RAKESH P PATEL
1
, TRIPTI HALDER
2
1
Department of Pharmaceutical Sciences, Shree S. K. Patel College of Pharmaceutical Education & Research, Ganpat University, Kherva,
Gujarat, India.
2
Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India. Email: meetbijit@gmail.com
Received: 02 February 2017, Revised and Accepted: 21 February 2017
ABSTRACT
Objective: The objective of this investigation was to develop and validates a new, rapid, accurate high performance liquid chromatographic (HPLC)
method for the quantification of besifloxacin hydrochloride.
Materials and Methods: Isocratic ultraviolet (UV)-HPLC separation was performed using a Zodiac C18 (150 mm × 4.6 mm) column, with 150 volume
of acetonitrile and 350 ml of methanol in 500 ml buffer as mobile phase at a flow rate of 2 ml/min and UV detection at 295 nm.
Results: The sample found stable for 24 hrs in analyte solution and compatible with a nylon filter. The Beer’s law plots were found to be linear over
the concentration range 70-130% with a correlation coefficient (r
2
) 0.9999 in diluent, phosphate buffer, and simulated tear media. The % relative
standard deviation was found <2% shows good precision, acceptable accuracy, and reproducibility of the new method for the determination of
besifloxacin hydrochloride.
Conclusion: The method was validated as per the ICH guidelines. The method is accurate and can be applied for qualitative analysis of besifloxacin
hydrochloride in bulk drug and in formulation.
Keywords: Besifloxacin hydrochloride, High performance liquid chromatographic, Stress testing, Validation, Linearity, Accuracy, Precision.
INTRODUCTION
Besifloxacin hydrochloride ((+)-7-[(3R)-3-aminohexahydro-1H-azepin-
1-yl]-8-chloro-1- cyclopropyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-
carboxylic acid hydrochloride) (Fig. 1) is a fourth generation, 8-chloro
fluoroquinolone type ophthalmic antibiotic used for the treatment
of bacterial conjunctivitis. Besifloxacin hydrochloride is a white to
pale yellowish-white powder. Besifloxacin hydrochloride ophthalmic
suspension 0.6% (Besivance™; Bausch & Lomb, Rochester, NY, USA)
was approved by the FDA in 2009 [1,2]. This drug and its formulation
is not official in any pharmacopeia and no official method was available
for the estimation of this drug in the pharmaceutical formulations.
The purpose of this proposed work was to develop and validate the
method using ultraviolet-high performance liquid chromatographic
(UV-HPLC) for quantification of besifloxacin hydrochloride. In
literature, other analytical methods described for the quantitative
analysis of besifloxacin hydrochloride but no report found using
UV-HPLC method [3-9]. The newly developed method was a unique
advantage over the other available methods, as it is simple, accurate,
precise, and specific for quantitative determination of besifloxacin
hydrochloride in pharmaceutical dosage form. This newly developed
method for quantification of besifloxacin hydrochloride was evaluated
in simulated eye tears, in buffer solution, and in diluent. The method
also validated after investigation of accuracy, reproducibility, stability,
and compatibility of the working condition of HPLC method according
to International Conference on Harmonization guidelines [10] and
IUPAC technical report [11].
MATERIALS AND METHODS
Materials
Inactive materials: Purified water obtained from a Milli-Q Gradient
water purification system (Millipore, Barnstead). All solvents used of
HPLC grade - acetonitrile, methanol (Source: Finar), triethylamine,
orthophosphoric acid (Source: Spectrochem), and other chemicals used
of analytical grade - ammonium dihydrogen phosphate, hydrochloric
acid, sodium chloride, sodium bicarbonate, calcium chloride, potassium
chloride (Source: Merck), sodium hydroxide, hydrogen peroxide
(30%) (Source: Rankem). Active material: Besifloxacin hydrochloride
was received from Indoco Remedies Limited, Mumbai, India and
was certified to contain 100.38% w/w. Besivance (besifloxacin
hydrochloride ophthalmic suspension 0.6%) was obtained by the
courtesy of Bausch & Lomb Incorporate. Other materials: Nylon filter of
25 mm diameter and 0.45 µ was procured from Axiva Sichem Biotech,
New Delhi, India.
Equipment
Besifloxacin hydrochloride was analyzed using high pressure liquid
chromatography (Agilent’s 1100 series HPLC system, USA) and
equipped with very sensitive a diode array detector. An analytical
balance from Mettler Toledo, USA, and an ultrasonic bath from Bandelin
Sonorex, Germany were used in the study.
Column and chromatographic conditions
The chromatographic separation was tested on Zodiac C18 (150 mm ×
4.6 mm), 5 µ column, Manufactured by Zodiac Life sciences. Using the
C18 column, the mobile phase used was acetonitrile: methanol (3:7).
The samples were monitored with UV detection at 295 nm at the flow
rate of 2 mL/min. The injection volume was 10 µl for all samples. The
column temperature was kept at 25°C.
Preparation of mobile phase and stock solutions
Buffer solution was prepared by mixing 3.45 g of ammonium
dihydrogen phosphate and 1.0 ml triethylamine in 1000 ml water. The
pH of solution adjusted to 3.0±0.05 with diluted orthophosphoric acid.
Mobile phase prepared by mixing 150 ml volume of acetonitrile and
350 ml of methanol. Diluent prepared by mixing 500 ml of water, 150 ml
of acetonitrile, and 350 ml of methanol. Test sample prepared by mixing
© 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.
org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2017.v10i5.17456
Research Article