AN UPDATED REVIEW ON ANALYTICAL METHODS FOR ESTIMATION OF AZELNIDIPINE
HTML Full TextAN UPDATED REVIEW ON ANALYTICAL METHODS FOR ESTIMATION OF AZELNIDIPINE
Kirankumar J. Gavali, Meenaxi Maruti Maste * and Nikhil S. Gawas
Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India.
ABSTRACT: Hypertension is a ubiquitous and serious worldwide health concern, having a dramatic influence on individual health outcomes. In light of this rising worry, Azelnidipine, a third generation long-acting dihydropyridine calcium channel blocker, has emerged as a prospective therapeutic treatment. A vast body of research has indicated that Azelnidipine produces a strong antihypertensive impact, especially in individuals diagnosed with essential hypertension, thus validating its therapeutic usefulness in controlling this prevalent illness. This thorough study strives to give an in-depth overview of the numerous analytical techniques applied for the measurement of Azelnidipine. It covers a variety of techniques, including spectroscopic UV analysis, as well as chromatographic methods such as reversed-phase high-performance liquid chromatography (RP-HPLC), high-performance thin-layer chromatography (HPTLC), and ultra-performance liquid chromatography (UPLC), either alone or in combination with other drugs. These methodologies together give useful insights into the reliable measurement of Azelnidipine in pharmaceutical formulations. These techniques are tested for accuracy, precision, and resilience according to ICH criteria. They are excellent for both bulk medication and tablet dose forms because to their simplicity, sensitivity, and reproducibility. This study emphasizes the merits and limits of several analytical approaches for Azelnidipine, giving significant insights for researchers.
Keywords: Azelnidipine, HPLC, HPTLC, Hypertension, UPLC, UV Spectrophotometry
INTRODUCTION: Azelnidipine is a dihydro-pyridine calcium channel blocker (CCB) employed in the treatment of hypertension and angina pectoris. Its chemical structure is reported as 3 - [1 - (Benzyldrylazetidin-3-yl)] - 5 - isopropyl - 2 - amino - 6 - methyl - 4 - (3-nitrophenyl) - 1, 4 dihydropyridine-3, 5-dicarboxylate, having a chemical formula of C33H34N4O6 and a molecular weight of around 583gm/mol 1. Azelnidipine is classified somewhat soluble in water, demonstrates solubility in methanol, ethyl acetate, acetone, acetic acid, and ethanol.
Azelnidipine acts by inhibiting transmembrane Ca2+ influx via voltage-dependent calcium channels in vascular smooth muscle. Calcium channels are divided into numerous categories, including L-type, T-type, N-type, P/Q-type, and R-type. By blocking L-type calcium channels, which are important for smooth muscle contraction and contribute to hypertension, Azelnidipine causes relaxation of the vascular smooth muscle, hence decreasing blood pressure 2.
Azelnidipine is listed in the Indian Pharmacopoeia, and different analytical techniques have been devised for its detection and quantification, such as spectrophotometry, HPLC, HPTLC and Bio-analytical. It is offered under several brand names, with formulations that may comprise Azelnidipine alone or in combination with other medicinal medicines, as mentioned in following tables.
FIG. 1: CHEMICAL STRUCTURES OF AZELNIDIPINE
TABLE 1: PHYSICOCHEMICAL PROPERTIES OF AZELNIDIPINE 3
| Mol. formula | C33H34N4O6 |
| Mol. Weight | 582.657 |
| Description | Yellow powder |
| Melting point | 193-195 |
| Solubility | Insoluble in water |
| A class of drug | Anti-Hypertensive |
| Metabolite | No active metabolite product. |
| Protein Binding | human plasma proteins (90%–91%) |
| Elimination Clearance | 26% in urine and 63% in feces over the 7 days post-dosing. |
| Half-life [T1/2] | 16 –28 hours |
TABLE 2: LIST OF TRADE NAMES OF AZELNIDIPINE
| Sr. no. | Brand Name | Name of the drug and Strength | Manufactured Company |
| 1 | Azovas®16 | Azelnidipine -16 mg | J.B. Chemicals and Pharmaceuticals Ltd –India |
| 2 | Azusa | Azelnidipine -16 mg, Azelnidipine – 8 mg | Ajanta Pharma Ltd – India |
| 3 | Azelikem 16Azelikem 8 | Azelnidipine -16 mg, Azelnidipine – 8 mg | Steris Healthcare Pvt. Ltd – India |
| 4 | Zeblong®16 | Azelnidipine -16 mg | IPCA Laboratories Ltd – India |
| 5 | Uniaz®16 | Azelnidipine -16 mg | Torrent pharmaceuticals Ltd – India |
| 6 | Azeldip™16 | Azelnidipine -16 mg | Glenmark Pharmaceuticals Ltd –India |
Mechanism: Azelnidipine acts by preventing the inflow of calcium ions (Ca2+) via voltage-gated channels in the smooth muscle cells of blood vessel walls. These calcium channels contain many varieties such as L-type, T-type, N-type, P/Q-type, and R-type. L-type calcium channels are especially crucial in this process. Typically, calcium ions cause the contraction of smooth muscles, which leads to elevated blood pressure (hypertension). By blocking calcium channels, Azelnidipine stops smooth muscle contraction, resulting to relaxation of the vascular walls and a drop in blood pressure 4.
Pharmacokinetic Profile: Azelnidipine is quickly and dose-dependently absorbed when taken orally. The mean peak plasma concentration (Cmax), which occurred 2.3 to 2.7 hours (tmax) following a single oral dosage of 5–15 mg, varied from 3 to 13.1 ng/mL in healthy adult volunteers who were fasting. From zero to infinity, the mean area under the plasma concentration-time curve (AUC) ranged from 27.5 to 135.8 mg/ml. The mean Cmax and AUC 24 h were 14.7 ng/mL and 81.6 mg/ml, respectively, after 7 days of taking an 8 mg dosage daily. The tmax on day 7 was 2.2 hours. By day two, steady-state concentrations were attained. Azelnidipine has a strong (about 90%) binding to plasma lipoproteins, according to in vitro research. Significant first-pass hepatic metabolism occurs with Azelnidipine, as it does with many calcium channel blockers.
Research on dogs and rats has shown that the parent substance is mostly digested since it is not found in faces or urine. Azelnidipine, as it does with many calcium channel blockers. Research on dogs and rats has shown that the parent substance is mostly digested since it is not found in faces or urine. Its metabolism is mostly mediated by cytochrome P450 (CYP) 3A4. After a daily dosage of 8 mg for seven days, the terminal elimination half-life of Azelnidipine is about 19.2 hours at steady state, and it is around 14–20 hours after a single oral dose of 5–15 mg in healthy volunteers 4.
The amount of Azelnidipine that is absorbed is increased when taken with meals, but the rate of absorption remains unaffected. When a single 10 mg dose of Azelnidipine was taken after a meal, the mean peak plasma concentration (Cmax) was 2.6 times higher than when taken in a fasted state (18.5 vs. 7.1 ng/mL, p < 0.05). Although the mean area under the curve (AUC) was 1.5 times higher after a meal (115.4 vs. 79.4 mg/ml), the difference was not statistically significant. The mean time to peak concentration (tmax) and half-life (t½) were not significantly different between the fed and fasted states (2.3 vs. 2.7 hours and 16.2 vs. 20.9 hours, respectively).
Therefore, the manufacturer recommends taking Azelnidipine with food. The pharmacokinetics of Azelnidipine in hypertensive patients are similar to healthy volunteers. In patients with mild-to-moderate hypertension, a single 8 mg dose resulted in a Cmax of 9.4 ng/mL and an AUC 24 h of 66.5 mg/ml. In elderly hypertensive patients (65-84 years), the same dose after a meal produced a Cmax of 15.8 ng/mL and an AUC24h of 107 mg/ml. After 7 days of 8 mg/day dosing, Cmax and AUC24h increased to 25.7 ng/mL and 242.8 m/ml, with a significant reduction in systemic clearance (640 mL/min vs. 1321 mL/min). (p < 0.05) 5, 6.
Pharmacodynamics Profile: Several studies have shown that Azelnidipine effectively lowers blood pressure. In a study of 10 patients with mild essential hypertension, 8 mg/day for 4 weeks reduced BP from 158/97 mm Hg to 145/90 mm Hg, without affecting heart rate, cardiac output, or hormone levels.
During exercise, it lowered BP while maintaining heart rate and vascular resistance, and improved left ventricular function. Azelnidipine (8-16 mg/day) also controlled BP over 24 hours, as shown by ambulatory blood pressure monitoring. In two studies, it significantly reduced both systolic and diastolic BP during daytime (p < 0.001) and night-time (p < 0.01). In another two studies, systolic BP was reduced at night (p < 0.05), with diastolic reductions not significant. Trough-to-peak ratios were 58% and 62%. In a study of 27 hypertensive patients, including those with renal dysfunction, Azelnidipine (8-16 mg/day) reduced BP significantly. In renal dysfunction patients, BP decreased by 24/18 mm Hg, and in those with renal parenchymal disease, by 21/16 mm Hg (p < 0.01 and p < 0.001, respectively) 7, 8, 9.
Adverse Reaction of Azelnidipine: The administration of teneligliptin is related with numerous undesirable effects, comprising, Headache, Dizziness or light-headedness Edema (swelling), particularly in the ankles or feet, Flushing, Fatigue, and Palpitations. There is less frequent adverse effect such as Hypotension (low blood pressure), gingival hyperplasia, Nausea or vomiting. Some significant response severe allergic responses (anaphylaxis), Liver dysfunction, Arrhythmia. Interaction with other drugs Azelnidipine may interact with other antihypertensive medicines, such as ACE inhibitors, beta-blockers, or diuretics, which may raise the risk of low blood pressure.
Methods for Estimation of the Azelnidipine: The determination of Azelnidipine in a given sample is commonly performed using a range of analytical methods extensively utilized in pharmaceutical research and quality control. Several widely used techniques for measuring Azelnidipine include UV-vis spectrophotometry Tables 3 and 4, Reversed-phase high-performance liquid chromatography (RP-HPLC, Tables 5 and 6), Ultraperformance liquid chromatography (UPLC, Table 7), High-performance thin-layer chromatography (HPTLC, Table 8), and Bioanalytical methods (Table 9).
Fig. 2 illustrates the articles reported for the estimation of Azelnidipine in percentage. These analytical methods collectively offer accurate and reliable evaluations of the compound’s presence and concentration in pharmaceutical formulations, thereby ensuring the quality and efficacy of pharmaceutical products. The accompanying tables provide a summary of the analytical techniques documented in the literature for the determination of Azelnidipine.
TABLE 3: SPECTROPHOTOMETRIC METHODS REPORTED FOR THE ESTIMATION OF AZELNIDIPINE AS SINGLE ENTITY
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | Azelnidipine UV spectrophotometric methods, | Matrices: API
Solvent: Acetone λmax (nm): 255 nm Linearity range: 2-14µg/ml LOD (µg /mL): 2.086 LOQ (µg/mL): 8.68 |
10 |
| 2 | Azelnidipine by uv-visible spectroscopy methods | Matrices: API & Tablet
Solvent: methanol λmax (nm): 257 nm Linearity range: 2-14µg/ml LOD (µg /mL): 0.77 LOQ (µg/mL): 2.36 |
11 |
| 3 | Azelnidipine by uv-spectrophotometric method | Matrices: Tablet
Solvent: methanol λmax (nm): 255 nm Linearity range: 2-14µg/ml LOD (µg /mL): 0.37 LOQ (µg/mL): 1.12 |
12 |
| 4 | Azelnidipine by uv-visible spectroscopy methods | Matrices: API
Solvent: methanol λmax (nm): 256 nm Linearity range: 10-50µg/ml |
13 |
| 5 | Azelnidipine by colourimetric methods | Matrices: API
Solvent: Ninhydrin, methanol, Glacial acetic acid. λmax (nm): 573 nm Linearity range: 2-14µg/ml LOD (µg /mL): 0.024 LOQ (µg/mL): 0.068 |
14 |
TABLE 4: REPORTED SPECTROPHOTOMETRIC METHODS FOR THE ESTIMATION OF AZELNIDIPINE WITH OTHER DRUGS
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | Azelnidipine / Telmisartan UV spectrophotometric methods, simultaneous method, Q-ratio method, and first derivative spectroscopy method. | Matrices: Tablet
Solvent: Methanol Detection Wavelength:255nm, TEL: 297nm Linearity: 2-12 µg/ml, TEL:10-50 µg/ml LOD: (µg/ml) simultaneous method- AZL:0.35, TEL:0.73Q-Absorption method- AZL:0.16, TEL:0.77First Derivative method- AZL:1.8, TEL:1.71 LOQ: (µg/ml) simultaneous method- AZL:0.927, TEL:2.16Q-Absorption method- AZL:0.048, TEL:2.34First Derivative method- AZL:5.4, TEL:5.16 |
15 |
| 2 | Azelnidipine and Valsartan/UV Spectroscopy, synthetic mixture | Matrices: API
Solvent: Methanol Detection Wavelength:240.00 nm, VAL:250.00 nm Linearity: 2-10 µg/ml, TEL:16-80 µg/ml |
16 |
| 3 | Azelnidipine / Metoprolol UV spectrophotometric methods, simultaneous method, q-absorbance ratio method, and first derivative spectroscopy method | Matrices: Tablet
Solvent: Methanol: Water Detection Wavelength: 257nm, MET: 223nm Linearity: AZL:1-10 µg/ml, MET:6.25-31.25 µg/ml LOD: (µg/ml) simultaneous method- AZL:0.088, MET:1.875Q-Absorption method- AZL:0.092, MET:1.770First Derivative method-AZL:0.085MET:1.825 LOQ: (µg/ml) simultaneous method- AZL:0.264, MET:5.625Q-Absorption method- AZL:0.276, MET:5.31First Derivative method-AZL:0.255, MET:5.475 |
17 |
| 4 | Azelnidipine and Metoprolol succinate, UV Spectrophotometric Methods | Matrices: Tablet
Solvent: Methanol: Distilled water Detection Wavelength: AZL:313nm, MET: 275.40nm |
18 |
TABLE 5: HPLC METHODS REPRESENTED FOR THE QUANTIFICATION OF AZELNIDIPINE AS SINGLE COMPONENT
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | Azelnidipine By RP-HPLC
Methods. |
Columns: C18 (250 mm x 4.6 mm i.d.,5 µ)
Mobile Phase: Acetonitrile: 0.5% triethyl amine (adjusted to pH 3.5 using orthophosphoric acid) (70:30 v/v). Wavelength: 254 nm Flow Rate: 1.0 ml/min Retention Time: 4.9 min |
19 |
| 2 | Azelnidipine By RP-HPLC
Methods. |
Columns: C8 Column
Mobile Phase: methanol: water (85:15 v/v). pH adjusted to 3.0using orthophosphoric acid Wavelength: 257 nm Flow Rate: 1.0 ml/min Retention Time: 9.1 min Linearity:0.5-25μg/ML LOD:0.15 μg/ML LOQ:0.5μg/mL |
20 |
| 3 | Azelnidipine By RP-HPLC
Methods. |
Columns: C8 Column
Mobile Phase: Methanol: Water (80: 20%v/v) o-phosphoric acid used for the Ph adjustment (pH-3). Wavelength: 257 nm Flow Rate: 1.0 ml/min Linearity: 20-100μg /ML LOD:0.2826μg/ML LOQ: 0.8566μg /mL |
21 |
| 4 | Azelnidipine By RP-HPLCMethods. | Columns: Water’s XBridge C18 column of particle size 5µ 250×4.6mm.
Mobile Phase: Potassium dihydrogen phosphate and orthophosphoric acid (buffer): Methanol (60:40v/v). Wavelength: 255 nm Flow Rate: 1.0 ml/min Retention Time:4.49min Linearity: 5-30μg /ML LOD: 1.38μg/ML LOQ: 4.17μg/mL |
22 |
| 5 | Azelnidipine By RP-HPLCMethods. | Columns: C18 (250×4.6mm.; 5 micron) column
Mobile Phase: Sodium dibasic Phosphate Buffer: Acetonitrile: Methanol in the ratio of (10:50:40 v/v/v) pH adjust 4.50 by o-phosphoric acid. Wavelength: 257 nm Flow Rate: 1.0 ml/min Retention Time:4.49min Linearity: 2-10μg /ML LOD: 0.75μg /ML LOQ: 2.75μg /mL |
23 |
TABLE 6: HPLC METHODS REPRESENTED FOR THE DETERMINATION OF AZELNIDIPINE IN COMBINED PHARMACEUTICAL PREPARATIONS
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | RP-HPLC Method Azelnidipine and Olmesartan | Columns:
Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 µm particle size) Mobile Phase: methanol, acetonitrile, and water in the ratio of 40:40:20 (by volume). Detection l (nm): 257 nm Flow Rate: 0.5 ml/min Retention Time: AZL-8.56min, OLE-3.04min Linearity: AZL-2-48 μg/ML, OLE-2.5-60 μg/ML |
24 |
| 2 | RP-HPLC–PDA Telmisartan and Azelnidipine
|
Columns:
Agilent C18 column (150 × 4.6 mm, 5) Mobile Phase: 0.1% V/V ortho phosphoric acid in water and acetonitrile (40:60 v/v) Detection l (nm): 260 nm Flow Rate: 0.5 ml/min Retention Time: AZL-2.2min, TLM-2.9min Linearity: AZL-2-12 μg/ML, TLM-20-120 μg/ML |
25 |
| 3 | RP-HPLC Method Azelnidipine and Telmisartan
|
Columns:
Inertsil C-18 Column with 150×4.6 mm×5 μm at column oven temperature 40°C, Mobile Phase: Acetonitrile and buffer in the ratio of 25: 75 (v/v) Detection l (nm): 254 nm Flow Rate: 1.5 ml/min Retention Time: AZL-2.2min, TLM-2.9min Linearity: AZL-20.14-60.42μg/ML, TLM-99.91299.73μg/ML LOD: AZL-11.21 μg/ML, TLM-2.75 μg/ML LOQ: AZL-33.96 μg/ML, TLM-8.35 μg/ML |
26 |
| 4 | RP-HPLC Method Azelnidipine and Metoprolol Succinate | Columns:
Hypersil ODS C185μ column (250 x4.6 mm) Mobile Phase: Acetonitrile: 0.025 M KH2PO4 Buffer (70:30 v/v, pH adjusted to 3with10% Ortho phosphoric acid. Detection l (nm): 228 nm Flow Rate: 1 ml/min Retention Time: Azelnidipine-3.281min, Metoprolol Succinate -10.799min Linearity: Azelnidipine-8-40μg/ML, Metoprolol Succinate-25-125μg/ML LOD: AZL-11.21 μg/ML, Metoprolol Succinate -2.75 μg/ML LOQ: AZL-33.96 μg/ML, Metoprolol Succinate -8.35 μg/ML |
27 |
| 5 | RP-HPLC Method Azelnidipine and Metoprolol Succinate | Columns:
Hibar ODS C185 µ column (250 x 4.6 mm) Mobile Phase: Methanol: water (70:30 v/v) as mobile phase (pH – 3.0) Detection l (nm): 230nm Flow Rate: 1.0 ml/min Retention Time: AZL-2.2min, Metoprolol Succinate -2.9min Linearity: Azelnidipine-8-40μg/ML, Metoprolol Succinate-25-125μg/ML |
28 |
| 6 | HPLC Method Azelnidipine and Telmisartan
|
Columns:
C18 Kromasil stationary column (5 µm, 250 mm × 4.6 mm) Mobile Phase: 0.1M NaH2PO4 solution (pH 3.5) and methanol at a comparative volume ratio of 50% each. Detection l (nm): 256nm Flow Rate: 1.0 ml/min Retention Time: AZL-4-12μg/ML TEL-20-60μg/ML Linearity: AZL-4-12μg/ML TLM-20-60μg/ML |
29 |
| 7 | HPLC Method Azelnidipine and Telmisartan
|
Columns:
250 mm length C18 column (Supelco, 4.6 mm inner diameter, 5.0 μm particle size) Mobile Phase: 0.1M Na2SO4 (pH 3.6) and acetonitrile (55% volume: 45% volume) Detection l (nm): 258nm Flow Rate: 1.0 ml/min Retention Time: AZL-3.178min TLM-2.225min Linearity: AZL-4-12μg/ML TLM-20-60μg/ML LOQ: AZL-0.0871 μg/ML, TLM-0.2516μg/ML |
30 |
| 8 | RP-HPLC Method Azelnidipine and Olmesartan Medoxomil | Columns:
Agilent Eclipse Plus (C18, 250 × 4.6 mm i.d., 5 μm) Mobile Phase: ethanol and 1% v/v aqueous acetic acid in the ratio of 49.5:50.5 Detection l (nm): 250 nm Flow Rate: 1 ml/min Retention Time: AZL-6.362min, OLM -3.323min Linearity: AZL-6.4-9.6 μg/ML OLM -16-24 μg/ML |
31 |
| 9 | RP-HPLC Method Azelnidipine and chlorthalidone | Columns:
Phenomenex Luna C8 column (250 × 4.6 mm, 5 µm particle size) Mobile Phase: acetonitrile and water, with the addition of 0.1 percent formic acid,acetonitrile concentration increased linearly from 30% to 55% v/v Detection l (nm): 256 nm Flow Rate: 1 ml/min Linearity: AZN-16-60 µg/mL CLN -25-100 µg/mL |
32 |
| 10 | RP-HPLC Method Azelnidipine and Metoprolol succinate
|
Columns:
Unesphere C18 column Agela Tech., (250 mm x 4.6 mm i.d., 5 μm,) Mobile Phase: Acetonitrile Phosphate Buffer pH 3.5 (40:60%v/v) Detection l (nm): 275 nm Flow Rate: 1 ml/min Retention Time: Azelnidipine-6.367min, Metoprolol Succinate -2.308min Linearity: Azelnidipine-10.0 - 30.0 μg/mL Metoprolol Succinate-50.0–150.0 μg/mL |
33 |
| 11 | RP-HPLC Method Azelnidipine and Telmisartan
|
Columns:
Intersil C18 column (250 × 4.6mm, i.d., 5μm) Mobile Phase: 70 volumes of acetonitrile and 30 volumes of 5 millimolar phosphate buffer pH 4.6. Detection l (nm): 255 nm Flow Rate: 1 ml/min Retention Time: Azelnidipine-6.367min, Telmisartan-2.308min Linearity: Azelnidipine-10-50 μg/mL Telmesartan-20-100μg/mL |
34 |
| 12 | RP-HPLC Method Azelnidipine and Olmesartan Medoxomil
|
Columns:
Agilent Eclipse Plus (C18, 250 × 4.6 mm i.d., 5 μm) Mobile Phase: ethanol and 1% v/v aqueous acetic acid in the ratio of 49.5:50.5 Detection l (nm): 250 nm Flow Rate: 1 ml/min Retention Time: Azelnidipine-6.362min, Olmesartan Medoxomil -3.323min Linearity: Azelnidipine-6.4-9.6 μg/mL Olmesartan Medoxomil -16-24 μg/mL |
35 |
| 13 | RP-HPLC Method Azelnidipine and Telmisartan
|
Columns:
Hyperchrom ODS C18 HPLC Column (252×4.6 nm) Mobile Phase: Buffer 0.05M Potassium dihydrogen orthophosphate (KH2PO4) Buffer (pH-4.0): Methanol (60:40) Detection l (nm): 215 nm Flow Rate: 1 ml/min Retention Time: Azelnidipine-5.69 min, Telmisartan -3.39 min |
36 |
| 14 | RP-HPLC Method Azelnidipine and Telmisartan
|
Columns:
C18 column (100 × 4.6 mm, 2.5 μm particle size) Mobile Phase: Acetonitrile: pH 3 phosphate buffer (75:25, v/v) Detection l (nm):237 nm Flow Rate: 0.9 ml/min Retention Time: Azelnidipine – 3.385min, Telmisartan – 6.415min Linearity: Azelnidipine-6.4-32 μg/mL Telmisartan -16-80 μg/mL |
37 |
TABLE 7: UPLC METHODS REPRESENTED FOR THE QUANTIFICATION OF AZELNIDIPINE WITH OTHER DRUGS IN PHARMACEUTICAL PREPARATIONS
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | RP-UPLC Telmisartan and Azelnidipine
|
Columns:
Agilent Zorbax Stable Bond (SB) packing C8 (100 mm × 2.1 mm, 2 μm) column Mobile Phase: 0.01 N potassium dihydrogen orthophosphate (pH 4.8) and acetonitrile in 70:30 v/v ratio. Detection l (nm): 257 nm Flow Rate: 0.3ml/min Linearity: Azelnidipine-2-12 μg/mL Telmisartan -20-120 μg/mL |
38 |
| 2 | RP-UPLC Telmisartan and Azelnidipine
|
Columns:
Acquity UPLC BEH C18 column (1.7 µm, 100 × 2.1 mm ID) Mobile Phase: Phosphate buffer: Acetonitrile in the ratio of 70: 30 v/v Detection l (nm): 240 nm Flow Rate: 0.3ml/min Retention Time: Azelnidipine-5.635 μg/mL Telmisartan -2.946 μg/mL |
39 |
TABLE 8: HPTLC METHODS REPRESENTED FOR THE ESTIMATION OF AZELNIDIPINE ALONE AND IN ITS COMBINED PHARMACEUTICAL FORMULATIONS
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | Azelnidipine/HPTLC | HPTLC: Silica gel 60 F254
Mobile Phase: Chloroform: Ethyl Acetate: Methanol in the ratio of 6.5:3.5:0.1 v/v/v Detection l (nm): 255 nm Rf value: 0.48±0.02 Linearity (ng/spot): 300–800 ng/band LOD: 58.035 ng/band LOQ: 175.86 ng/band |
40 |
| 2 | Azelnidipine and Chlorthalidone HPTLC
|
HPTLC: silica gel 60 F254 TLC plate
Mobile Phase: chloroform, ethyl acetate, and methanol in the ratio of 6.5:3.5:0.6 (by volume). Detection l (nm): 240 nm Rf value: Azelnidipine: 0.67 ± 0.02 Chlorthalidone: 0.24 ± 0.02 |
41 |
| 3 | Azelnidipine and Telmisartan HPTLC | HPTLC: Silica gel 60 F254
Mobile Phase: Toluene: Acetonitrile: Formic acid (5:4.5:0.5 % V/V/V) Detection l (nm): 255 nm Linearity (ng/spot): Azelnidipine: 200-700 ng/ band Telmisartan: 1000-3500 ng/band LOD: Azelnidipine-24.71 ng/band LOQ: Azelnidipine- 74.90 ng/band LOD: Telmisartan: 175.04 ng/band LOQ: Telmisartan: 530.44 ng/bank |
42 |
TABLE 9: BIOANALYTICAL METHODS REPRESENTED FOR THE QUANTIFICATION OF AZELNIDIPINE ALONE AND IN COMBINED PHARMACEUTICAL FORMULATION
| Sr. no. | Drugs /Method | Method characterization | Ref. no. |
| 1 | Azelnidipine & Olmesartan Medoxomil in human plasma RP-HPLC | Matrix: human plasma
Internal standard: N/A Stationary phase: BDS Hypersil C18, 250 mm X 4.6 mm, 5µ analytical column. mobile phase: Acetonitrile: Water, pH adjusted with ortho-phosphoric acid in the ratio 60:40 Flow rate: 1ml/min. Detection l (nm): 256nm Linearity: Azelnidipine- 0.5 to 12 µg /ml Olmesartan Medoxomil- 1 to 15 µg/ml |
43 |
FIG. 2: PERCENTAGE ESTIMATION OF AZELNIDIPINE IN REPORTED STUDIES
Merits and Demerits of the Studies: The method proposed by Panda M et al. (2023) is simple, rapid, accurate, precise, and validated, with no interference from excipients and a wide linearity range. However, challenges include method transferability, ongoing regulatory compliance, and potential interference in more complex formulations. The RP-HPLC method introduced by Raimalani J et al. (2023) adheres to ICH guidelines for method validation, ensuring rigorous standards for accuracy, precision, specificity, and robustness, which enhances its credibility for regulatory and routine analysis. However, the method faces challenges such as complex development, time-consuming sample preparation, and environmental concerns regarding solvent disposal. The HPTLC method developed by Akshay S. Rane et al. (2022) serves as a stability-indicating assay, enabling accurate measurement of Azelnidipine even in the presence of degradation products, thereby ensuring reliable stability testing. Nevertheless, challenges include issues with solvent disposal, limited throughput, potential interference from complex formulations, subjectivity in manual evaluation, and the need for further optimization under various stress conditions.
Challenges: Challenges include complex Mobile phase requirements and potential specificity limitations, with a summary of methods in Table 10.
TABLE 10: KEY FEATURES OF ANALYTICAL METHODS FOR AZELNIDIPINE
| Study | Most Commonly Used Method | Challenges | Merits |
| Ahmed A et al (2022) 13 | RP-HPLC | Complex mobile phase composition | Precise and accurate estimation, adherence to ICH guidelines |
|
Panda M et al (2023) 34 |
RP-HPLC |
Transferability, maintaining regulatory compliance, and addressing interference from complex formulations. | simple, rapid, accurate, precise, and validated, with no interference from excipients and a wide linearity range |
|
Raimalani J et al. (2023) 32 |
RP-HPLC |
Complex development, lengthy sample preparation, and solvent disposal concerns. |
The method complies with ICH validation guidelines, ensuring high standards of accuracy, precision, specificity, and robustness, enhancing its credibility for regulatory and routine use. |
|
Akshay S Rane et al. (2022) 40 |
HPTLC |
Low throughput, interference from complex formulations, subjective manual evaluation, and the need for further optimization. | Stability-indicating, accurately measuring Azelnidipine amid degradation products, ensuring reliable stability testing. |
CONCLUSION: In conclusion, Azelnidipine has established itself as a key therapeutic agent in the management of hypertension. This review provides a thorough examination of the drug's pharmacological properties, pharmacokinetic profile, chemical structure, safety considerations, and mechanism of action. Furthermore, it offers an overview of the various analytical techniques employed for the quantification of Azelnidipine, including UV spectroscopy, HPLC, HPTLC, UPLC and other advanced methodologies. RP-HPLC emerges as the most commonly utilized technique due to its high precision, accuracy, and reliability. However, challenges such as the complexity of mobile phase compositions, stringent method requirements, and potential interference from excipients or other formulation components may limit its broader application in routine analysis. Despite these challenges, the reviewed studies highlight the effectiveness of RP-HPLC and other analytical techniques in providing accurate quantification of Azelnidipine, thus advancing pharmaceutical analysis. Further research and optimization of these methods are essential to address these limitations. Additionally, the current methods have not incorporated a systematic approach, such as Design of Experiments (DoE), particularly for single-drug estimation of Azelnidipine. Future developments should prioritize method validation through a Quality by Design (QbD) approach to ensure a more robust, reliable, cost effective, and efficient process for pharmaceutical analysis.
ACKNOWLEDGMENTS: The authors are thankful to Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Belagavi, 590010, Karnataka, India.
CONFLICT OF INTEREST: The authors have no conflicts of interest regarding this investigation.
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How to cite this article:
Kumar JK, Maste MM and Gawas NS: An updated review on analytical methods for estimation of azelnidipine. Int J Pharm Sci & Res 2025; 16(7): 1755-66. doi: 10.13040/IJPSR.0975-8232.16(7).1755-66.
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IJPSR
Kirankumar J. Gavali, Meenaxi Maruti Maste * and Nikhil S. Gawas
Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India.
meenaximaste@klepharm.edu
08 January 2025
21 January 2025
22 January 2025
10.13040/IJPSR.0975-8232.16(7).1755-66
01 July 2025
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