Al-Zoman Nourah Zoman, Maher Hadir Mohamed, Al-Subaie Amal
College of Pharmacy, Department of Pharmaceutical Chemistry, King Saud University, P.O. Box 22452, Riyadh, 11495 Saudi Arabia.
College of Pharmacy, Department of Pharmaceutical Chemistry, King Saud University, P.O. Box 22452, Riyadh, 11495 Saudi Arabia ; Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, 21521 Egypt.
Chem Cent J. 2017 Jan 3;11:1. doi: 10.1186/s13065-016-0232-6. eCollection 2017.
Ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak) are the newest medicines approved for use in the treatment of hepatitis C virus (HCV) and are available in tablet form as an oral combination. Specifically, these agents are indicated in the treatment of HCV in patients with genotype 1 infection. Due to the therapeutic importance and increased use of Viekira Pak, proper methods for its determination in bulk and pharmaceutical formulations must be developed.
The present study describes the development and validation of a simple, rapid, selective and economical reverse phase high performance liquid chromatography-diode array detection (HPLC-DAD) method for the simultaneous determination of paritaprevir (PAR), ombitasvir (OMB), dasabuvir(DAS) and ritonavir (RIT) in bulk and pharmaceutical preparations. The proposed method was carried out using an RPC column (150 × 4.5 mm, 3.5 μ), with a mobile phase consisting of 10 mM phosphate buffer (pH 7)and acetonitrile (35:65, v/v) at a flow rate of 1 ml/min and a detection wavelength of 254 nm. Sorafenib (SOR) was selected as the internal standard to ensure that the quantitative performance was high. The method was validated based on its specificity, linearity, limit of detection, limit of quantitation, accuracy, precision, robustness and stability. The calibration curves for PAR, DAS, RIT and OMB were linear at 2.5-60, 1.25-30, 1.7-40 and 0.42-10 μg/ml, respectively, and all of the correlation coefficients were >0.999.
The proposed method was successfully applied for the determination of ombitasvir/paritaprevir/ritonavir/dasabuvirin tablets, without interference from the excipient peaks. Hence, the method can be applied for the routine quality control analysis of the studied drugs, either in bulk or dosed forms.Graphical abstractSimultaneous estimation of newly developed antiviral agents in pharmaceutical formulations by HPLC-DAD method.
奥比他韦/帕立普韦/利托那韦/达沙布韦（Viekira Pak）是最新获批用于治疗丙型肝炎病毒（HCV）的药物，以口服复方片剂形式提供。具体而言，这些药物适用于治疗基因型1感染的HCV患者。鉴于Viekira Pak的治疗重要性及其使用的增加，必须开发出在原料药和药物制剂中测定其含量的合适方法。
本研究描述了一种简单、快速、选择性强且经济的反相高效液相色谱 - 二极管阵列检测（HPLC - DAD）方法的开发与验证，该方法用于同时测定原料药和药物制剂中的帕立普韦（PAR）、奥比他韦（OMB）、达沙布韦（DAS）和利托那韦（RIT）。所提出的方法采用RPC柱（150×4.5 mm，3.5μm），流动相由10 mM磷酸盐缓冲液（pH 7）和乙腈（35:65，v/v）组成，流速为1 ml/min，检测波长为254 nm。选择索拉非尼（SOR）作为内标以确保定量性能良好。该方法基于其特异性、线性、检测限、定量限、准确度、精密度、稳健性和稳定性进行了验证。PAR、DAS、RIT和OMB的校准曲线分别在2.5 - 60、1.25 - 30、1.7 - 40和0.42 - 10μg/ml范围内呈线性，所有相关系数均>0.999。
所提出的方法成功应用于测定片剂中奥比他韦/帕立普韦/利托那韦/达沙布韦，不受辅料峰的干扰。因此，该方法可用于所研究药物的原料药或剂型的常规质量控制分析。
通过HPLC - DAD法同时测定药物制剂中新型抗病毒药物。
