A Comprehensive Review of Analytical Methods of Ritonavir

 

Aakanksha C. Kumbhar, Prerana B. Gherade, Sandhyarani S. Sonkamble,

 Kumudini R. Pawar

Department of Pharmaceutical Quality Assurance, Abhinav College of Pharmacy,

Narhe, Pune, 411041.

 

ABSTRACT:

Ritonavir, a potent antiretroviral agent, plays a crucial role in the management of human immunodeficiency virus (HIV) infections. As its therapeutic importance grows, the need for accurate and reliable analytical methods to assess the quality and purity of ritonavir becomes paramount. This review aims to provide a comprehensive overview of the various analytical techniques employed for the quantification, identification, and characterization of ritonavir in pharmaceutical formulations. This review aims to assist researchers, pharmaceutical professionals, and regulatory authorities in selecting the most appropriate analytical methods for ritonavir analysis.

 

 

 

INTRODUCTION:

Ritonavir is a protease inhibitor used to treat HIV/AIDS. It is rarely used for its antiviral activity, instead serving as a booster for other protease inhibitors. Although ritonavir was originally developed to inhibit the HIV protease, studies have shown that it also inhibits cytochrome P450-3A4.¹ Because of its mechanism of action, ritonavir is currently being studied for use in treating some types of cancer. It is also combined with other medicines to treat hepatitis C infection.²

 

 

In this activity, indications, dosing, administration, side effect profile, mechanisms of action, toxicity, and contraindications for ritonavir as part of the treatment of HIV/AIDS will be reviewed. This activity is relevant to members of the interprofessional team involved in the care of patients living with HIV/AIDS, including physicians, infectious disease specialists, nurses, pharmacists, physician assistants, and other healthcare providers.³

 

IUPAC name:

1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl) methyl] carbamoyl] amino] butanoyl] amino]-1,6-diphenylhexan-2-yl] carbamate.⁴

 

Molecular weight: 720.9, Formula: C37H48N6O5S2

Structure:

 

Figure 1: Structure of Ritonavir.⁴

 

MECHANISM OF ACTION:

Ritonavir is a protease inhibitor used in the treatment of HIV/AIDS. Its mechanism of action involves binding to the active site of the HIV protease enzyme, inhibiting its activity. By doing so, ritonavir disrupts the final stages of the viral replication cycle, preventing the cleavage of long chains of viral proteins and the formation of mature, infectious viral particles. This inhibition leads to the accumulation of immature and non-functional viruses, reducing the overall viral load in the body and slowing down the progression of the HIV infection.⁵ Ritonavir is often employed in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART) to effectively manage HIV/AIDS. Additionally, it serves as a booster for other protease inhibitors, enhancing their levels in the blood and improving their efficacy.^6,7

 

ANALYTICAL TECHNIQUES IN PHARMACEUTICAL ANALYSIS:

Numerous analytical techniques, including UV/Visible Spectrophotometry (UV)^8,9, High-Performance liquid chromatography(HPLC)¹⁰, Ultra high-performance liquid chromatography(UPLC)¹¹, High-performance thin layer chromatography (HPTLC)^12,13,14,15, Bio-analytical studies¹⁶, Mass spectrometry (MS)^17,18,19, Nuclear Magnetic Resonance (NMR)²⁰, Fourier Transform Infrared (FTIR) spectroscopy^21,22,23 were identified in the literature for the estimation of RTV in bulk and pharmaceutical formulations as well as in biological samples. In the current review, estimation of RTV was discussed for a variety of dosage forms as a single constituent and in combination with many anti-retroviral medications.²⁴

 

SUMMARY OF ANALYTICAL METHODS USED FOR RITONAVIR:

Table 1: Analytical methods development and validation for Ritonavir in combined and single dosage formed by UV-visible spectroscopy and RP-HPLC

Sr. No	Drug/Drugs	Method	Description	Ref.
1	Lopinavir and Ritonavir	New sensitive UV spectrophotometric method for simultaneous estimation in fixed-dose combination as soft gels	Wavelength: Lopinavir: 258nm, Ritonavir: 245nm Solvent: Methanol and 0.1 N HCl Linearity: Lopinavir: 10-30µg/mL, Ritonavir: 2-10µg/mL	25,26
2	Ritonavir	UV-derivative spectrophotometric determination of capsules and comparison with LC method	Wavelength: Second-derivative spectra: 222.3 nm Solvent: Methanol Linearity:10-30 µg/mLCorrelation coefficient: 0.9995	27
3	Ritonavir and Lopinavir	SimultaneousUV spectrophotometric method for estimation in bulk and tablet dosage form	Wavelength: Method A (Absorbance maxima method): Lopinavir:260 nm, Ritonavir:238 nm Method B (Area Under Curve): Lopinavir:250- 270 nm, Ritonavir:228-248 nm Solvent: Dis. water Linearity: Lopinavir:100-500 µg/mL, Ritonavir:10-35µg/ml	28
4	Darunavir and Ritonavir	Simultaneous method development, validation and stress studies of in bulk and combined dosage form using UV spectroscopy	Wavelength: Darunavir:267 nm, Ritonavir:240 nm Solvent: Methanol Linearity: Darunavir:2-18μg/ml, Ritonavir:5- 100μg/ml	29
5	Ritonavir	Development and validation of UV-visible spectrophotometric method for estimation in bulk and formulation	Wavelength:255nm Solvent: Water: Methanol (40:60 v/v) Linearity:30-210 µg/mL Correlation coefficient: 0.999	30
6	Ritonavir	Development and validation of spectrophotometric method for quantitative estimation in bulk and pharmaceutical dosage forms	Wavelength: Method A (Absorbance maxima) = 239 nm Method B (First order derivative spectra) = 232 nm Solvent: Water: Methanol (40:60 v/v) Linearity:10-50 μg/mL	31,32
7	Ritonavir and Lopinavir	Analytical methods development and validation for simultaneous estimation in pharmaceutical formulation by simultaneous equation method using UV spectrophotometry	Wavelength: Lopinavir:257.5 nm, Ritonavir:240.0 nm Solvent: Acetonitrile: Water (30:70v/v) Linearity: Lopinavir:80-180µg/ml, Ritonavir:10-60 µg/ml Correlation coefficient: Lopinavir:0.998, Ritonavir:0.997	33
8	Ritonavir	Spectrophotometric determination in bulk and pharmaceutical formulation	Wavelength:242nm Solvent: Methanol Linearity:10-20 μg/mL	34
9	Ritonavir	Method development, validation and forced degradation studies of drug using Uv-visible spectroscopy	Wavelength:239nm Solvent: Methanol: Acetonitrile Linearity:10-60 μg/mL Correlation coefficient: 0.9999	35
10	Ritonavir and Lopinavir	Method development and validation for the simultaneous determination by RP-HPLC and by UV- spectrophotometry	RP-HPLC Wavelength:225nm Mobile phase: Methanol: Water (85:15) Flow rate: 1ml/min Linearity: Lopinavir:20-200µg/ml, Ritonavir:5-50µg/ml Retention time: Ritonavir:4.8, Lopinavir: 5.9 min UV-spectrophotometric: Lopinavir:245 nm, Ritonavir:219 nm Linearity: Lopinavir:20-200µg/ml, Ritonavir:10-50µg/ml	36
11	Atazanavir and Ritonavir	Development and validation of UV spectroscopic by Q-absorption ratio, RP-HPLC method for simultaneous estimation in bulk and pharmaceutical dosage form	RP-HPLC Wavelength:250nm Mobile phase: Acetonitrile: Acetate buffer (60:40v/v) Linearity: Atazanavir:  5–35 μg/ml, Ritonavir: 10-60 µg/ml UV-Spectrophotometric: Atazanavir:250nm, Ritonavir: 239.4 nm Linearity: Atazanavir:3-150µg/ml, Ritonavir:1-50 µg/ml Correlation coefficient:0.999.	37,38
12	Ritonavir	Analytical methods for the quantification in pharmaceuticals a comparative evaluation	RP-HPLC Wavelength:235nm Mobile phase: 20 mM KH2PO4 (pH 3): Acetonitrile (45:55 v/v) Flow rate:1.2 mL/min Linearity: Ritonavir:5-50µg/ml Retention time: Ritonavir: 4.8, Lopinavir: 5.9 min UV-spectrophotometric: Ritonavir:235nm Solvent: Ethanol Linearity: Ritonavir:10-50µg/ml	39
13	Ritonavir	A new robust analytical method development, validation, and stress degradation studies by UV-spectroscopy and HPLC methods	RP-HPLC Wavelength:275nm Mobile phase: Acetonitrile: 0.1% Formic acid (1:1 v/v) Flow rate:1.0 ml/min Linearity: Ritonavir:25-150 µg/ml UV-spectrophotometric: Ritonavir:273nm Linearity: Ritonavir:10-60 µg/ml	40
14	Ritonavir	Method development, validation and stability study in bulk and pharmaceutical dosage form by spectrophotometric method	Wavelength: First-order derivative method= 253.2nm Linearity:4-20 μg/mL Correlation coefficient: 0.9981 Area under curve method=237 - 242nm Linearity:4-20 μg/mL Correlation coefficient:0.9992	41
15	Ritonavir	Development and validation of new analytical methods in bulk and pharmaceutical dosage forms	Wavelength: PDA detector= 239 nm Mobile phase: Acetonitrile: Ortho phosphoric acid (55:45 v/v) Flow rate: 1ml/min, Linearity: 8.0– 240µg/ml Correlation Coefficient: 0.99982	42
16	Ritonavir	Development and validation of spectrophotometric method in tablet dosage form	Wavelength: Amplitude difference: Absorbance maxima=     246nm, Absorbance minima= 266 nm Solvent: Methanol, Linearity: 10-30 μg/mL	43
17	Ritonavir and Darunavir	UV-spectrophotometric absorbance correction method and absorbance ratio method: simultaneous estimation	Wavelength: Method A (Absorbance Ratio Method): Ritonavir:239nm MethodB (Absorbance correction method) = 251nm and 267 nm Linearity:10-50 μg/ml	44
18	Valacyclovir HCl monohydrate and Ritonavir	Spectrophotometric method development and validation in bulk and tablet dosage: absorption ratio method	Wavelength: Valacyclovir hydrochloride monohydrate:237.52 nm, Ritonavir:256.75 nm Solvent: 0.1M Hydrochloric acid (HCl) Linearity: Valacyclovir hydrochloride monohydrate:10–20mg/mL, Ritonavir:10–20 mg/mL Correlation Coefficient: Valacyclovir hydrochloride monohydrate:0.995, Ritonavir:0.994	45
19	Atazanavir and Ritonavir	Spectrophotometric simultaneous determination in combined tablet dosage form by ratio derivative and AUC method	Ratio spectra derivative: Atazanavir:280.01 nm, Ritonavir:286.12 nm Area under curve:246.97-252.03 nm and 240.78-244.16 nm Solvent: Methanol Linearity: Atazanavir:15-75µg/mL, Ritonavir:5-25 µg/mL.	46
20	Nirmatrelvir and Ritonavir	Development and validation of a new RP-UPLC methodin bulk and tablet dosage forms: simultaneous estimation	Wavelength: 267 nm (PDA detector) Mobile phase: Acetonitrile: Triethyl amine (30:70 v/v) Flow rate:0.5 mL/min Retention time: Nirmatrelvir: 1.262 min, Ritonavir: 1.873 min Linearity: Nirmatrelvir: 37.5-225 µg/mL, Ritonavir: 25-150 µg/mL Correlation coefficient: Nirmatrelvir: 0.99956, Ritonavir: 0.9998	47,48
21	Ritonavir, Ombitasvir and Paritaprevir	RP-HPLC method for simultaneous estimation in tablet dosage forms and their stress degradation studies	Wavelength: 254 nm (PDA detector) Mobile phase:0.01N % w/v Potassium di-hydrogen orthophosphate buffer (pH 3.0): Acetonitrile Flow rate: 1 mL/min Retention time: Nirmatrelvir: 1.262 min, Ritonavir: 1.873 min Linearity: Ombitasvir: 3.125-18.75 µg/ml, Paritaprevir: 18.75–112.5 µg/ml, Ritonavir: 12.5-75 μg/ml	49
22	Ritonavir	An RP-HPLC method for the estimation in pharmaceutical dosage forms	Wavelength:210 nm UV detection Mobile phase: Acetonitrile: Methanol 80:20(V/V) Flow rate: 1ml/min, Linearity: 10-100ppm Retention time:3.38 min	50
23	Ritonavir	Reverse phase HPLC method for determination in pharmaceutical preparations	Wavelength:239nm (PDA detector) Mobile phase: Acetonitrile: Potassium Dihydrogen Phosphate andDipotassium Hydrogen Ortho Phosphate (45: 55, v/v) Flow rate: 1ml/min, Linearity: 20-120 ug/ml	51
24	Ritonavir and Darunavir	QbD tool–evaluated stability-indicating UPLC method for the determination of drugs used to treat HIV	Wavelength:266nm (PDA detector) Mobile phase: Methanol: 0.01 M phosphate buffer (pH 4.0) [60:40 v/v] Flow rate:0.2 ml/min, Correlation coefficient: 0.999	52
25	Nirmatrelvir and Ritonavir	Adjusted green HPLC determination in the new FDA-approved co-packaged pharmaceutical dosage using supported computational calculations	Wavelength:215nm (UV detector) Mobile phase: Ethanol: Water (80:20 v/v) Flow rate: 1 ml/min Retention time: Nirmatrelvir: 4.9, Ritonavir: 6.8 Linearity: 10-20 ug/ml	53
26	Nirmatrelvir and Ritonavir	Development and validation of the RP-HPLC method in bulk and pharmaceutical formulation: simultaneous estimation	Wavelength:272nm Mobile phase:0.01M Potassium dihydrogen phosphate buffer: Acetonitrile (45:55 v/v) Flow rate: 1 ml/min, Retention time: Nirmatrelvir: 4.9, Ritonavir: 6.8 Linearity: Nirmatrelvir: 75-225 ug/ml, Ritonavir: 50-150 μg/mL	54
27	Ritonavir	Method development and validation in tablet dosage form by using Rp-High-Performance Liquid Chromatography	Wavelength:253nm (PDA detector) Mobile phase:0.1% Formic acid: Acetonitrile (65:35) Flow rate: 1ml/min, Linearity: 20-120 ug/ml Correlation coefficient: 0.999	55
28	Ombitasvir, Paritaprevirand Ritonavir	Stability-indicating method development and validation for simultaneous estimation in formulation by Ultra-Performance Liquid Chromatography	Wavelength: 252 nm Mobile phase:0.01N Potassium dihydrogen orthophosphate (pH 5.3): Methanol (60:40%v/v), Flow rate: 0.3 mL/min Retention time: Ombitasvir: 1.765, Paritaprevir: 2.192 min, Ritonavir: 1.326 min	56
29	Ritonavir	Development and Validation of RP-HPLC method for quantification of total, free and entrapped in lipid nanocarriers and drug content of film-coated fixed-dose formulation	Wavelength:242nm (UV detection) Mobile phase: Orthophosphoric acidin water (pH 3.0): Acetonitrile Flow rate: 1.2ml/min Linearity: 0.25 µg/mL to 16 µg/mL	57
30	Nirmatrelvir and Ritonavir	Development of a Simple accurate method, validation and its degradation studies in bulk and marketed formulation by RP-HPLC	Wavelength:258nm (UV detection) Mobile phase: Acetonitrile: Buffer containing hexane sulphonic acid (50:50 v/v) Flow rate: 1ml/min Retention time: Nirmatrelvir: 2.481, Ritonavir: 3.873	58
31	Lopinavir and Ritonavir	Quantitative estimation in tablets by RP-HPLC Method	Wavelength:240nm UV detection Mobile phase: Buffer (pH4.5): Acetonitrile (45:55 v/v) Flow rate: 1.2ml/min	59
32	Lopinavir and Ritonavir	Novel validated UPLC method for quantitation in bulk and p’ceutical formulation with its impurities	Wavelength:215nm (PDA detection) Mobile phase: Acetonitrile: Methanol (85:15) Flow rate: 0.4ml/min	60
33	Lopinavir and Ritonavir	Development and validation of an analytical method by HPLC	Wavelength:254nm (UV detection) Mobile phase: Acetonitrile: Methanol:  0.01M Potassium dihydrogen orthophosphate buffer (pH 3.0) [30:20:50v/v/v] Flow rate: 1ml/min	61
34	Atazanavir and Ritonavir	Method development and validation by RP HPLC method for estimation of antiviral combination as in bulk and pharmaceutical dosage form	Wavelength:273nm (UV detection) Mobile phase: Acetonitrile: Water (80:20 v/v) (pH 3.0) Flow rate: 1ml/min Correlation coefficients:Atazanavir: 0.9998, Ritonavir: 0.999 Retention time: Atazanavir: 2.95 min, Ritonavir: 6.86 min	62
35	Ombitasvir Paritaprevir Ritonavir Dasabuvir	Simultaneous determination of newly developed antiviral agents in pharmaceutical formulations by HPLC-DAD	Wavelength:254nm Mobile phase:10 mM phosphate buffer (pH 7): Acetonitrile (35:65, v/v), Flow rate: 1ml/min Linearity: Paritaprevir: 2.5–60, Dasabuvir:1.25–30, Ritonavir1: 7–40, Ombitasvir 0.42–10 ug/ml Correlation coefficients:0.999	63
36	Darunavir And Ritonavir	Development and validation of a new analytical method for the simultaneous estimation in pharmaceutical dosage form	Wavelength:293nm Mobile phase: Buffer 0.1% Formic acid: Acetonitrile (70:30) Flow rate: 0.95 ml/min Retention time: Darunavir: 2.369min, Ritonavir: 2.911 min	64
37	Lopinavir and Ritonavir	RP – HPLC method for simultaneous estimation of antiretroviral drugs in tablet dosage form	Wavelength:240nm Mobile phase: Acetonitrile:  Triethylamine (0.5%) (pH 5.0 adjusted with glacial acetic acid) (67:33v/v) Flow rate: 1.2 ml/min Retention time: Lopinavir: 5.235min, Ritonavir: 8.265min Linearity: Lopinavir: 40-200ug/ml, Ritonavir: 10-50ug/ml	65
38	Atazanavir and Ritonavir	An analytical method development and validation for simultaneous estimation of tablet dosage forms by using UPLC	Wavelength:249nm Mobile phase: Phosphate buffer (40%andpH 2.5): Acetonitrile (60%), Flow rate: 1.2 ml/min Retention time: Atazanavir: 0.819, Ritonavir: 1.236 min Linearity: Atazanavir: 30 to 90 mg/ml, Ritonavir: 10 to 30 mg/ml	66
39	Ritonavir and Darunavir	Stability indicating RP-HPLC method for simultaneous estimation in bulk and its synthetic mixture	Wavelength:220nm Mobile phase: Phosphate buffer (pH 3.5): (Acetonitrile and Methanol 5:1) (30:70 v/v), Flow rate: 1 ml/min Retention time: Darunavir: 2.813 min, Ritonavir: 2.126 min Linearity: Ritonavir: 20 – 100μg/ml, Darunavir: 120 - 600 μg/ml	67
40	Darunavir and Ritonavir	A new UPLC method for the separation and quantitation of process and degradation-related impurities in the combined dosage tablets form	Wavelength:240nm Mobile phase: A (potassium dihydrogen phosphate, disodium hydrogen phosphate: Tetra N-butyl ammonium hydrogen sulfate in water; pH 6.5) B (Acetonitrile: Tetrahydrofuran 90:10 v/v)	68
41	Atazanavir and Ritonavir	Simultaneous quantification of in pharmaceutical dosage form by validated RP-HPLC method	Wavelength:240nm Mobile phase: Phosphate buffer (pH3.4): Acetonitrile (45:55) Flow rate: 1 ml/min Retention time: Atazanavir: 2.7 min, Ritonavir: 3.9 min Linearity: Ritonavir: 12.5 - 125µg/ml, Atazanavir: 37.5 - 375µg/ml	69

Table 2: Analytical methods development and validation for Ritonavir in combined and single dosage formed by LC-MS-MS

Sr.No	Drug/Drugs	Method	Description	Ref.
1	Nirmatrelvir and Ritonavir	Simultaneous quantification of LC-MS/MS in patients treated for COVID-19	Chromatographic condition:C18-column Detected by: Tandem mass spectrometry Internal standard: Methanol: Water (50:50 v/v) Linearity: Nirmatrelvir: 10 – 10000 ng/ml, Ritonavir: 2 – 2000 ng/mL	70
2	Ritonavir	Development and validation of a simple, sensitive, selective and stability-indicating RP-UPLC method for the quantitative determination of ritonavir and its related compounds	Chromatographic condition:RP18 (100 × 2.1 mm, 1.7 μm) column Wavelength:240 nm (photodiode array detector) Mobile phase: Potassium dihydrogen phosphate: Acetonitrile Flow rate:0.5 mL/min Detected by: Tandem mass spectrometry	71
3	Ritonavir	LC-MS/MS studies of drug and its forced degradation products	Chromatographic condition: Waters XTerra C (18) column (250 mm x 4.6 mm i.d., 5 micron) Mobile phase: Water: Methanol: Acetonitrile (40:20:40, v/v/v)	72
4	Ritonavir	Development and validation of a systematic UPLC–MS/MS method for simultaneous determination of three phenol impurities	Chromatographic condition: BEH C18 column (100 mm × 2.1 mm, 1.7 μm) Mobile phase:0.05% Ammonia: Methanol: 5.0 mM Ammonium acetate buffer (30:70, v/v) Flow rate:0.2 mL/min, Ionizer: Positive electrospray ionization, Correlation Coefficient:0.9998	73
5	Atazanavir, Darunavir and Ritonavir	Validation of simultaneous quantitative method of HIV protease inhibitors in human plasma by UPLC-MS/MS	Chromatographic condition: Waters Acquity UPLC C18 (50 × 2.1 mm, 1.7 μm) column Mobile phase: 10 mM Ammonium formate (pH 4.0): Acetonitrile Linearity: Atazanavir: 5.0–6000 ng/mL, Darunavir: 5.0–5000 ng/mL, Ritonavir: 1.0–500 ng/mL	74
6	Lamivudine, Zidovudine, Lopinavir, and Ritonavir	Assessment of plasma levels in HIV-positive pregnant women drug monitoring application to improve patient safety UPLC-ESI-MS/MS	Chromatographic condition:C18 column (2.1 μm*50 mm, 1.7 μm) Mobile phase: Acetonitrile: Formic acid (0.1%) Linearity: Lamivudine: 50–3,000 ng/mL, Zidovudine: 75–4,500 ng/mL, Lopinavir: 250–15,000 ng/mL, Ritonavir: 25–1,500-ng/Ml	75
7	Ritonavir	LC-MS/MS studies and its forced degradation products	Chromatographic condition:C18 column (250mm × 4.6mm i.d., 5um) Mobile phase: Water: Methanol: Acetonitrile (40:20:40, v/v/v)	76

 

Table 3: Analytical methods development and validation for Ritonavir in combined and single dosage formed by HPTLC

Sr.No.	Drug/Drugs	Method	Description	Ref.
1	Lopinavir and Ritonavir	HPTLC method for simultaneous determination of capsule dosage form	Wavelength: 263nm TLC plate: Aluminum-backed silica gel 60F254 Mobile phase: Toluene: Ethyl Acetate: Methanol: Glacial acetic acid (7.0:2.0:0.5:0.5) Linearity: Lopinavir: 6.67-20.00 µg/spot, Ritonavir: 1.67 to 5.00 µg/spot	77
2	Lopinavir and Ritonavir	Stability indicating HPTLC method for estimation of fixed-dose combination tablets	UV detection: 266 nm Mobile phase: Benzene: Ethanol: Acetic acid (7:3: 0.4% v/v) Linearity: Lopinavir: 800-4800 ng/band, Ritonavir: 200- 1200 ng/ band	78,79
4	Lopinavir and Ritonavir	Simultaneous HPTLC determination of in combined dosage form	Wavelength:266 nm TLC plate: Aluminum sheets of silica gel 60F-254 Mobile phase: Ethyl acetate: Ethanol: Toluene: Diethylamine (7:2.0:0.5:0.5 v/v/v/v) Linearity: Lopinavir: 8-20 μg/ml, Ritonavir: 2- 10 μg/ml	80,81
5	Ritonavir and Lopinavir	Simultaneous Determination in Combined Tablet Dosage Form by HPTLC Method	aluminium plates pre-coated with silica gel 60 F254 aluminium plates pre-coated with silica gel 60 F254 aluminium plates pre-coated with silica gel 60 F254 aluminium plates pre-coated with silica gel 60 F254 aluminium plates pre-coated with silica gel 60 F254 10 cm × 10 cm aluminum plates precoated with 250-µm layers of silica gel 60 F254 Wavelength:210 nm TLC plate: Aluminum plates pre-coated with silica gel 60 F254 Mobile phase: Toluene: Ethyl acetate: Methanol: Glacial acetic acid (7:2:0.5:0.5 v/v/v/v) Linearity: Ritonavir:400-2400 ng spot-1, Lopinavir: 1600-9600 ng spot-1	82, 83, 84
6	Lopinavir and Ritonavir	Development and validation of the HPTLC Method of simultaneous analysis in their combined tablet dosage formed	Wavelength:210 nm Mobile phase: Chloroform: 1, 4 - Dioxane (7:3 %v/v) TLC plate: Silica gel GF aluminum Rf value: Lopinavir 0.74, Ritonavir 0.58 Linearity: Lopinavir: 160-960 ng/spot, Ritonavir 40-240 ng/spot	85
7	Molnupiravir, Favipiravir and Ritonavir	Highly sensitive high-performance thin-layer chromatography method for the simultaneous determination in pure forms and pharmaceutical formulations	TLC plate: Silica gel 60F254 Mobile phase: Chloride: Ethyl acetate: Methanol: 25% Ammonia (6:3:4:1, v/v/v/v) Wavelength: 289 nm Rf value: Favipiravir: 0.22, Molnupiravir: 0.42, Ritonavir: 0.63 Linearity: Molnupiravir: 3.75–100.00 μg/mL, Favipiravir: 3.75–100.00 μg/mL, Ritonavir: 2.75–100.00 μg/mL	86
8	Atazanavir sulfate and Ritonavir	Statistical correlation and simultaneous estimation of in fixed dosage form by high-performance LC and HPTLC	Wavelength:254 nm TLC plate: pre-coated silica gel 60F254 aluminum plates Mobile phase: Toluene: Methanol: Glacial acetic acid: Ethyl acetate (7:0.5:1.5:2, v/v/v/v) Linearity: Atazanavir: 30–300 ng/spot, Ritonavir10–100 ng/spot	87
9	Lopinavir Ritonavir	Stability-indicating HPTLC method for simultaneous determination of in bulk and pharmaceutical dosage form	TLC plate: Silica Tab 60F254 Merck plates Mobile phase: Toluene: Ethyl acetate: Methanol (7:2:0.5:0.5v/v/v) Wavelength: 254 nm Rf value: Lopinavir: 0.32 ± 0.05, Ritonavir: 0.48± 0.05 Linearity: Lopinavir: 200- 1000 ng/band, Ritonavir: 200-1000 ng/band	88
10	Ritonavir	Separation identification and characterization of acidic degradation under ICH recommended stress condition by HPTLC MS/TOF	TLC plate: precoated silica gel 60F254 HPTLC plates Mobile phase: Acetonitrile: Methanol: Water (5:3.5:2.5 v/v)	89
11	Lopinavir and Ritonavir	Validated HPTLC method for simultaneous determination in-tablet dosage form	TLC plate: Aluminum HPTLC plate (20×10cm) precoated with silica gel F254 Mobile phase: Toluene: Ethyl acetate: Methanol: Formic acid (6:4, 4.5:0.5:0.5v/v/v/v) Wavelength: 254nm Linearity: Lopinavir: 2- 12μg/spot, Ritonavir: 2 - 6 μg/spot	90
12	Ritonavir	Validated stability indicating HPLC and HPTLC methods for the determination of ritonavir in bulk powder and in capsules	TLC plate: Fluka TLC aluminum sheets of silica gel Densitometric measurement: Spots 240 nm Fluorescent indicator: 254nm Mobile phase: Acetonitrile: Water (1:2 v/v) pH 5.0 Rf: 0.41 ± 0.014	91
13	Atazanavir and ritonavir	Simultaneous estimation in-tablet dosage form by HPTLC method	TLC plate: Silica gel 60G F254 Mobile phase: Toluene: Ethyl acetate: 0.1% Formic acid (6.0:4.0:1.0 v/v) Linearity: Atazanavir: 150-900 ng/spot, Ritonavir: 50-300 ng/spot	92

 

CONCLUSION:

The present review discussed different analytical approaches employed for the assessment of Ritonavir. This review aims to assist researchers, pharmaceutical professionals, and regulatory authorities select the most appropriate analytical methods for ritonavir analysis.

 

CONFLICT OF INTEREST:

The authors declare that there are no conflicts of interest regarding the publication of this review article.

 

ACKNOWLEDGEMENTS:

We would like to extend our heartfelt gratitude to the Principal of Abhinav Education Society’s, College of Pharmacy (B. Pharm) for their invaluable support and guidance throughout the preparation of this review article.

 

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Received on 20.01.2024      Revised on 05.04.2024 Accepted on 25.05.2024      Published on 10.12.2024 Available online on December 30, 2024 Asian Journal of Pharmaceutical Analysis. 2024; 14(4):283-292. DOI: 10.52711/2231-5675.2024.00050 ©Asian Pharma Press All Right Reserved