Int J Chem Res, Vol 5, Issue 2, 1-4Review Article


MINI REVIEW: INSIGHTS ON INSTRUMENTAL ANALYSIS OF OMBITASVIR, PARITAPREVIR AND RITONAVIR

ROSHDY E. SARAYA1, MAGDA ELHENAWEE2, HANAA SALEH2, MAHMOUD M. SEBAIY3*

1Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt, 2,3Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
Email: mmsebaiу@zu.edu.eg

Received: 19 Dec 2020 Revised and Accepted: 01 Feb 2021


ABSTRACT

In this literature review, we will introduce most of the up-to-date reported methods that have been developed for the determination of Ombitasvir, Paritaprevir and Ritonavir in their pure form, combined form with other drugs combined form with degradation products, and in biological samples. Most of reported methods includes spectrophotometric and chromatographic methods specially HPLC and HPTLC.

Keywords: HCV, Ombitasvir, Paritaprevir, Ritonavir, Degradation products, Biological samples


INTRODUCTION

Infection due to hepatitis C virus (HCV) is a leading cause for severe chronic liver disease, which can result in progressive liver damage such as cirrhosis and hepatocellular carcinoma. HCV is a single-stranded virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States and affecting 72% of all chronic HCV patients [1]. Ombitasvir (OMB) is an inhibitor of NS5A, a protein essential for viral replication and virion assembly. The barrier for the development of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAD [2]. In addition, the combination of OMB, the ritonavir-boosted PI paritaprevir, and the non-nucleoside polymerase inhibitor dasabuvir with or without ribavirin was approved for patients with HCV genotype 1 [3]. Treatment with direct acting antivirals such as OMB is associated with very minimal side effects, with the most common being headache and fatigue; Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [4]. Paritaprevir (PAR) prevents viral replication by inhibiting the NS3/4A serine protease of HCV. Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 and its activating cofactor Nonstructural Protein 4A are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B [5].

As such, in this literature review, we will introduce most of the up-to-date reported methods that have been developed for the determination of OMB, PAR and RIT in different matrices.

Fig. 1: Chemical structures of ombitasvir (OMB), paritaprevir (PAR), and ritonavir (RIT), Ombitasvir (OMB)

Review of analytical methods

Various techniques were used for the analysis of OMB in pure forms, in their pharmaceutical formulations and in biological fluids. The available reported methods in the literature can be summarized as follows:

Table 1: Chromatographic methods for determination of OMB

Matrix Column Mobile phase System Ref.
Plasma UPLC BEH C18 Ammonium acetate 5 mmol (pH 9.5): ACN (gradient elution). UHPLC–MS/MS  [6]
Tablet Hypersil BDS C18 column 0.01N % mmol phosphate buffer (pH 3) and acetonitrile (35:65, v/v). HPLC-DAD 254 nm [7]
plasma Intersil ODS C18 20% ACN: 20% Methanol, 60%1 mmol NH4H2PO4 Buffer (PH 6.5). HPLC-UV 230 nm [8]
Liver Waters Acquity BEH C18 column A gradient elution with 0.1% FA in water and ACN. UHPLC–MS/MS [9]

Other methods

A novel micellar electrokinetic capillary chromatographic (MEKC) method was developed for the simultaneous determination of OMB, PAR, RIT and dasabuvir (DAS). The technique was based on the separation of all of the selected drugs in a deactivated fused silica capillary with a background electrolyte solution (BGE) composed of 25 mM phosphate buffer with 30 mM sodium dodecyl sulphate (SDS) (the pH of the aqueous phase was adjusted to 8) mixed with ethanol in a ratio of 65:35 (v/v). The capillary and sample temperature was maintained at 24 °C, and the detection was performed at 239 nm. The electrophoresis was performed by applying a high voltage (30 kV) to the capillary [10].

Paritaprevir (PAR)

Review of analytical methods

Various techniques were used for the analysis of PAR in pure forms, in their pharmaceutical formulations and in biological fluids. The available reported methods in the literature can be summarized as follows:

Table 2: Chromatographic methods for determination of PAR

Matrix Column Mobile phase System Ref.
Plasma UPLC BEH C18 Ammonium acetate 5 mmol (pH 9.5) and acetonitrile (gradient elution). UHPLC–MS/MS  [6]
Tablet Hypersil BDS C18 column 0.01N % mmol phosphate buffer (pH 3) and acetonitrile (35:65, v/v). HPLC-DAD 254 nm [7]
Rat liver Acquity BEH C18 A gradient elution with (95:5:0.1v/v/v), water: acetonitrile: formic acid and (acetonitrile containing 0.1% formic acid). UPLC–MS/MS [11]
plasma Intersil ODS C18 20% Acetonitrile, 20% Methanol, 60%1 mmol NH4H2PO4 Buffer (PH 6.5). HPLC-UV 230 nm [8]
Liver Waters Acquity BEH C18 A gradient elution with 0.1% FA in water and ACN. UHPLC–MS/MS [9]

Ritonavir (RIT)

Review of analytical methods

Various techniques were used for the analysis of RIT in pure forms, in their pharmaceutical formulations and in biological fluids. The available reported methods in the literature can be summarized as follows:

Table 3: Spectrophotometric methods for determination of RIT

Drugs Method or reagent λmax Ref
RIT and Atazanavir (ATV) Ratio spectra derivative method, Area under curve method. 280.01 nm(ATV), 286.12 nm(RIT), 246.97-252.03 nm (ATV): 240.78-244.16 nm(RIT) [12]
RIT First-order derivative method, under curve method.

253.2 nm (RIT)

237-242 nm (RIT)

[13]
RIT and lopinavir First-order derivative method. 246.70 nm (RIT) and 278.10 nm (lipinavir) [14]
Sofosbuvir, Lamivudine, and RIT Silver nanoparticles synthesis. 421 nm for Sofosbuvir and RIT and at 425 nm for Lamivudine [15]

Chromatographic methods for determination of RIT

Table 4: HPLC methods for determination of RIT

Matrix Column Mobile phase System Ref.
Plasma UPLC BEH C18 Ammonium acetate 5 mmol (pH 9.5) and acetonitrile (gradient elution). UHPLC–MS/MS  [6]
Tablet Hypersil BDS C18 column 0.01N % mmol phosphate buffer (pH 3) and acetonitrile (35:65, v/v). HPLC-DAD 254 nm [7]
Plasma Aquasil® C18 A gradiant elution with 0.05% formic acid in either water or methanol. HPLC–MS/MS [16]
Rat liver Acquity BEH C18 A gradient elution with (95:5:0.1v/v/v),water: acetonitrile: formic acid and (acetonitrile containing 0.1% formic acid). UPLC–MS/MS [11]
plasma Intersil ODS C18 20% Acetonitrile, 20% Methanol, 60%1 mmol NH4H2PO4 Buffer (PH 6.5). HPLC-UV 230 nm [8]
Liver Waters Acquity BEH C18 column A gradient elution with 0.1% FA in water and ACN. UHPLC–MS/MS [9]
Plasma OmniSpher C18 column A gradient elution with ACN: 50 mmol/l potassium phosphate (pH 5.75). HPLC-UV at 215 nm [17]
Plasma C18 column ACN: 50 mmol phosphate buffer (pH 5.63) (40:60, v/v). HPLC-UV at 215 nm [18]
Plasma C18 Column Acetonitrile plus distilled water within25 mmol sodium acetate and 25 mmol hexane-1-sulfonic acid and adjusted to pH 6.0 (40.5:59.5, v/v). HPLC-UV at 239 nm [19]
Plasma NovaPak C18 column ACN, methanol and tetramethylammonium perchlorate in dilute aqueous TFA (45: 5: 50 v/v/v). HPLC-UV at 205 nm [20]
Plasma C18 column ACN, methanol and 0.01 M tetramethylammonium perchlorate in 0.1% aqueous TFA (40: 5: 55 v/v/v). HPLC-UV at 205 nm [21]
Plasma Inertsil ODS column ACN: 5 mmol ammonium acetate buffer (pH 3.5) (80: 20 v/v). HPLC–MS/MS [22]
Tablet phenomenex-Luna C18 Acetonitrile: 0.5% TEA (pH 5) (67:33 %, v/v). HPLC-DAD at 205 nm [23]
Plasma Waters UPLC C18 column 10 mmol AF (pH 4.0) adjusted with FA: methanol (10:90 v/v). UPLC–MS/MS [24]
Tablet A symmetry C18 Phosphate buffer (pH 4): ACN (50:50). HPLC-UV at 239 nm [25]
Plasma Acquity UPLC C18 0.1% FA: methanol (40:60, v/v). UPLC–MS/MS [26]
Tablet a Hypersil BDS-C18 Phosphate buffer (pH3.4): ACN (50:50, v/v). HPLC-UV at 250 nm [27]
Tablet Waters UPLC C18 column A gradient elution with 0.01 M potassium dihydrogen phosphate (pH 3.5): ACN UPLC–MS/MS [28]
Tablet a Waters Symmetry C18 ACN: 2 mmol ammonium acetate containing 0.01% FA (v/v) (70:30 v/v). HPLC–MS/MS [29]
Tablet An Agilent TC-C18 Methanol: ACN: water in the (35:41.5:23.5 v/v/v). HPLC-UV at 222 nm [30]
Tablet a Thermo Hypersil C18 0.05M KH2PO4 buffer (pH3.0): ACN (45:55 v/v). HPLC-UV at 254 nm [31]
Tablet An Agilent TC-C18 ACN: 0.05 M phosphoric acid (55: 45, v/v). HPLC-UV at 240 nm [32]
Tablet a C18 column 0.06 M SDS: 1‐pentanol (pH 7) (97.5: 2.5 v/v). HPLC-UV at 214 nm [33]
Tablet Symmetry C18 phosphate buffer (pH 4.0): ACN (45:55 % v/v). HPLC-UV at 237 nm [34]
tablet RP-C18 Kinetix core-shell column (0.15 M sodium lauryl sulfate and 0.01 M sodium dihydrogen phosphate, pH 6.2) and ethanol (56:44). HPLC-Uv at 254 [35]

Table 5: HPTLC methods for determination of RIT

Matrix Column Mobile phase System Ref.
Tablet, vials, and plasma silica-gel 60 F254 plate Chloroform‒methanol‒ethyl acetate (6:2:2 v/v). UV-302 nm [35]
Tablet silica-gel 60 F254 plate Ethyl acetate: ethanol: toluene: diethylamine (7:2.0:0.5:0.5, v/v/v/v). UV-266 nm [36]
Tablet silica-gel 60 F254 plate Ethyl acetate: Toluene: methanol (7.5: 2: 0.5 v/v/v). UV-234 nm [37]
Tablet silica-gel 60 F254 plate Chloroform: ethyl acetate: acetone (5:2:3, v/v/v). UV-244 nm [38]

CONCLUSION

This literature review represents an up to date survey about all reported methods that have been developed for determination of Ombitasvir, Paritaprevir and Ritonavir in their pure form, combined form with other drugs, combined form with degradation products, and in biological samples such as liquid chromatography, spectrophotometry, electrochemistry, etc.

FUNDING

Nil

AUTHORS CONTRIBUTIONS

All the authors have contributed equally.

CONFLICT OF INTERESTS

Declared none

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