Determination of ofloxacin in tear by HPLC-ESI-MS/MS method: comparison of ophthalmic drug release between a new mucoadhesive chitosan films and a conventional eye drop formulation in rabbit model.
Ofloxacin, second-generation fluoroquinolone derivative, is one of the most commonly used to treat and prevent superficial ocular infection in animals and human beings. However, poor bioavailability, rapid elimination, and non compliance by patients are several problems associated with ocular route. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions, while reducing the side effects and the toxicity associated with frequent applications. Specific analytical methods to determine drugs in eye are needed to analyze and compare the new controlled release ocular devices with those conventional eye drops. The topical eye administration of ophthalmic drugs induces lachrymation, and the tear promotes a drug wash out. Quantify drugs in tear is a good tool to study their kinetic comportment in the eye. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantitation of ofloxacin in rabbits' tears was developed and validated. The tear was collected with tear strips, extracted by a liquid extraction procedure and then separated on an ACE C(18) column with a mobile phase composed of 0.15% aqueous formic acid and methanol (60:40, v/v). Calibration curve was constructed over the range of 10-5000 ng/mL for ofloxacin. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%, respectively. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the ofloxacin concentration in tears of rabbits treated with a mucoadhesive chitosan films and a conventional eye drop formulation.
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil. ricardobyrro@bol.com.br
Ricardo Martins Duarte
RM
Byrro
Gustavo
G
de Oliveira Fulgêncio
Armando
A
da Silva Cunha
Isabela Costa
IC
César
Paula Rocha
PR
Chellini
Gerson Antônio
GA
Pianetti
D000268:Adhesiveness; D060433:Administration, Ophthalmic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005561:Formates / Q000737:chemistry; D057230:Limit of Detection; D008297:Male; D000432:Methanol / Q000737:chemistry; D023421:Models, Animal; D015242:Ofloxacin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D011817:Rabbits; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards; D013666:Tears / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005561:Formates; D009883:Ophthalmic Solutions; C030544:formic acid; D048271:Chitosan; D015242:Ofloxacin; D000432:Methanol