Stability Study and Validated Reversed Phase Liquid Chromatographic Method for the Determination of Tirofiban Hydrochloride in Presence of Tyrosine as a Process Impurity

Abstract

Tirofiban hydrochloride was subjected to the degradation under conditions of hydrolysis (acidic and alkaline degradation), oxidative, thermal and photolytic degradation as prescribed by ICH. A simple and precise liquid chromatographic method has been developed and validated for the simultaneous determination of tirofiban hydrochloride monohydrate (TIR) and its synthetic starting material; tyrosine (TRS). All the chromatographic separations were achieved on Zorbax SB C18, 250 mm×4.6 mm i.d., 5μm column at a flow rate of 1 mL min −1. Isocratic elution based on 0.1 M phosphate buffer (pH 3) -acetonitrile (70:30, v/v) with UV detection at 227 nm was applied. For the stability study separation of TIR from its degradation products was achieved using 0.1 M phosphate buffer (pH 3) -acetonitrile (72:28, v/v) with UV detection at 210 nm. Method validation parameters namely, linearity, accuracy and precision were found to be acceptable over the concentration ranges of 10-250 µg mL -1 for TIR and 1-70 µg mL -1 for TRS. The minimum detection limits were 1.76 µg mL -1 for TIR and 0.13 µg mL -1 for TRS. The optimized method was validated and proved to be specific, robust and accurate for the quality control of the cited drug in drug substance and drug product.

Novel Copper Oxide-Integrated Carbon Paste Tirofiban Voltammetric Sensor

“…Herein, the base hydrolysis of TIR performed at 75 °C for 30 min revealed degradation of 40% of the parent compound, while the corresponding acidic degradation resulted in 32% degradation. Oxidative degradation with H 2 O 2 caused 50% degradation which comes in agreement with previously reported values . None of the degradation products exhibited electrochemical activity or voltammetric peaks near that recorded for TIR; therefore, the presented analysis protocol can be considered as the stability-indicating analysis protocol.…”

“…Oxidative degradation with H 2 O 2 caused 50% degradation which comes in agreement with previously reported values. 11 None of the degradation products exhibited electrochemical activity or voltammetric peaks near that recorded for TIR; therefore, the presented analysis protocol can be considered as the stability-indicating analysis protocol.…”

“…TIR is unofficial in pharmacopeia; moreover, only few chromatographic and spectrometric approaches were reported to monitor TIR residues in bulk, dosage forms, and biological fluids. Chromatographic methods based on HPLC-UV, RP-HPLC, − and liquid chromatographic-mass spectrometry (LC–MS) ,, were found in the literature. The chiral separation chromatographic method utilizing hydroxypropyl-γ-cyclodextrin (HP-γ-CD) as the chiral mobile phase was evaluated for selective separation of TIR enantiomers in samples with UV detection at 226 nm .…”