title: A Validated RP-HPLC Method for the Analysis of 1-Fluoronaphthalene and Its Process-Related Impurities.
abstract: A simple and precise reversed-phase high-performance liquid chromatography method was developed and validated for the determination of 1-fluoronaphthalene and its process-related impurities, 1-aminonaphthalene, 1-nitronaphthalene, naphthalene and 2-fluoronaphthalene. 1-Fluoronaphthalene is the key starting material for the synthesis of duloxetine hydrochloride active pharmaceutical ingredient and is therefore a potential impurity of the API. The determination of the impurity profile is critical for the safety assessment of a substance and manufacturing process thereof. In duloxetine hydrochloride active pharmaceutical ingredient, only 1-fluoronaphthalene is detected and neither of its related impurities of 1-aminonaphthalene, 1-nitronaphthalene, naphthalene and 2-fluoronaphthalene. Chromatography was carried out on a Symmetry C18 (250 × 4.6 mm, 5 μm) column, using mobile phase A-a mixture of 0.01 Μ KH2PO4 buffer (pH 2.5 ± 0.1):methanol:acetonitrile in the ratio of 35:52:13 v/v/v and mobile phase B-a mixture of methanol:acetonitrile in the ratio of 80:20 v/v at a flow rate of 1.0 mL/min. The analytes were monitored using photo diode array detector at 230 nm. The proposed method is found to be having linearity in the concentration of 0.075-5.000 μg/mL, 0.150-5.000 μg/mL, 0.3125-5.000 μg/mL and 0.3125-5.000 μg/mL for 1-aminonaphthalene, 1-nitronaphthalene, naphthalene and 2-fluoronaphthalene, respectively, with correlation coefficients of 0.9998, 0.9998, 0.9997 and 0.9997, respectively. The proposed method was validated as per the International Conference on Harmonization guidelines. The mean recoveries for all the studied impurities are in the range of 90-110%. Due to its specificity, high precision and accuracy, the developed method can be used for the determination of 1-fluoronaphthalene, key starting material for the synthesis of duloxetine hydrochloride API.
authors.affiliation: Pharmathen, API Operations Unit, Building Thermi 1, 9th km Thessaloniki - Thermi, P.O. Box 60499, GR 570 01, Thessaloniki, Greece egkaragiannidou@pharmathen.com.
authors.forename: Evrykleia G
authors.initials: EG
authors.lastname: Karagiannidou
authors.affiliation: Pharmathen, API Operations Unit, Building Thermi 1, 9th km Thessaloniki - Thermi, P.O. Box 60499, GR 570 01, Thessaloniki, Greece.
authors.forename: Eleni T
authors.initials: ET
authors.lastname: Bekiari
authors.affiliation: Pharmathen, API Operations Unit, Building Thermi 1, 9th km Thessaloniki - Thermi, P.O. Box 60499, GR 570 01, Thessaloniki, Greece.
authors.forename: Elli I
authors.initials: EI
authors.lastname: Vastardi
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D009281:Naphthalenes / Q000032:analysis* / Q000737:chemistry*; D015203:Reproducibility of Results
chemical_list: D009281:Naphthalenes; C042963:1-fluoronaphthalene