Content uploaded by Nidhi Nitin Chauhan
Author content
All content in this area was uploaded by Nidhi Nitin Chauhan on Mar 02, 2021
Content may be subject to copyright.
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
682
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
AN ANALYTICAL APPROACH OF AZELNIDIPINE: A REVIEW
Drashti Mandale*, Rujuta Mistry and Dr. Nidhi Chauhan
Department of Quality Assurance, Laxminarayan Dev College of Pharmacy, Bharuch.
ABSTRACT
Azelnidipine (AZEL) is chemically (±)-3-(1-diphenylmethylazetidin3-
yl) 5-isopropy12-amino-1, 4-dihydro-6-methyl-4-(3-nitrophenyl) 3,5-
pyridinedicarboxylate. It is a dihydropyridine (DHP) type of calcium
channel blocker (CCB) used for the treatment of hypertension. AZEL
has two enantiomers due to an asymmetric carbon at the 4-position of
the DHP ring. The pharmacological action of AZEL resides in the (R)-
enantiomer. This is in marked contrast to other CCBs in which the (S)-
enantiomer is responsible for the biological activity. The peculiar
three-dimensional structure of the active enantiomer of AZEL may be
related to its unique pharmacological features that are not shared by
other DHPs such as long lasting reduction in blood pressure, decreased heart rate and
antiatherosclerotic effect. AZEL also shows diuretic effect by increasing urine volume and
thus reduction in retention of ions. Some analytical methods for the quantitative
determination of Azelnidipine in pharmaceutical formulations like UV, LCMS/MS, RP-
HPLC, HPLC-MS/MS, UFLC, LC-ESI-MS
KEYWORDS: Azelnidipine, hypertension, UV, LCMS/MS, RP-HPLC, HPLC-MS/MS,
UFLC, LC-ESI-MS
INTRODUCTION
Hypertension is a condition where blood pressure is elevated to an extent that clinical benefit
is obtained from BP lowering. Hypertension is one of the most important risk factor for both
coronary artery disease and cardiovascular disease.[1] Azelnidipine was synthesized by Ube
Industries, Ltd. and developed by Sankyo Co., Ltd. (currently known as Daiichi Sankyo Co.,
Ltd., Tokyo, Japan) and was launched into the market as CALBLOCK in Japan in 2003. The
drug has renoprotective effects (such as reducing proteinuria by dilating efferent arterioles),
as well as cardioprotective, insulin resistance-improving, cerebroprotective, and
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 10, Issue 3, 682-692 Review Article ISSN 2278 – 4357
*Corresponding Author
Prof. Drashti Mandale
Department of Quality
Assurance, Laxminarayan
Dev College of Pharmacy,
Bharuch.
Article Received on
02 Jan. 2021,
Revised on 23 Jan. 2021,
Accepted on 12 Feb. 2021
DOI: 10.20959/wjpps20213-18460
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
683
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
antiatherosclerotic effects. Azelnidipine occurs as two enantiomers due to an asymmetric
carbon at the 4-position of the 1,4 dihydropyridine ring.[2] Azelnidipine (AZEL) (3-[1-
(diphenylmethyl)azetidin-3-yl] 5-propan-2-yl 2-amino-6-methyl-4-(3-nitrophenyl)-1,4-
dihydropyridine-3,5-dicarboxylate) is a new dihydropyridine derivative with calcium
antagonistic activity. Azelnidipine is inhibits trans membrane Ca+2 influx through the
voltage dependent channels of smooth muscle in vascular walls. They enter the cells through
cell membrane, lower peripheral vascular resistance and arterial pressure. It is used for
treatment of essential hypertension and angina pectoris.[3]
Figure: Chemical structure of AZEL.
Drug Profile[4,5]
Table 1: Chemical Profile of AZEL.
Sr No
Parameters
Azelnidipine
1
Molecular weight
582.646 g/mol
2
Molecular formula
C33H34N4 O6
3
CAS No
123524-52-7
4
Melting point
122 - 123°C
5
pKa
7.89
6
Solubility
Slightly soluble in methanol, freely soluble in acetone,
soluble in ethyl acetate, sparingly soluble in water
7
storage
Stored in tightly closed container in cool, dry and well
maintained area.
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
684
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
Table 2: Pharmacokinetic Profile of AZEL.
Parameters
Azelnidipine
Absorption
Orally absorbed
Metabolism
Metabolized by cytochrome P450 (CYP) 3A4
in the liver and has no active metabolite
Bioavailability
Less than 50%
Half life
16 - 24 hrs
Cmax
3.0 - 13.1 ng/ml
Plasma protein binding
≈90%
Mechanism of action[6]
Azelnidipine is Ca+2 channel blocker inhibits trans membrane Ca+2 influx through the
voltage dependent channels of smooth muscle in vascular walls. Ca+2 channels are classified
into various categories including L-type, T-type, N-type, P/Q- type, R-type Ca+2 channels.
Normally, calcium induces smooth muscle contraction, contributing to hypertension. When
calcium channels are blocked, the vascular smooth muscle does not contract, resulting in
relaxation of vascular smooth muscle walls and decreased BP.
Marketed formulations of Azelnidipine
Table 3: Marketed formulation of Azelnidipine.
Sr No
Brand Name
Company Name
Formulation
Dose (mg)
1
Azovas
JB Chemicals and
Pharmaceuticals Ltd
Tablet
8, 16
2
Calblock
Daiichi Sankyo
healthcare co ltd
Tablet
8, 16
An analytical approach for determination of Azelnidipine
Kunti d. Raskapur* and coworkers[7] have reported UV method for the determination of
Azelnidipine in tablet dosage form. For this a simple and reproducible UV
spectrophotometric method was developed for the assay of Azelnidipine from tablet
formulation. The solvent system and wavelength of detection were optimized in order to
maximize the sensitivity of the proposed method. The method is developed using a
SHIMADZU 1800 UV‐VISIBLE spectrophotometer with 1.0 cm matching quartz cells were
used for absorbance measurements. The UV spectra were recorded over the wavelength 200‐
400 nm. Azelnidipine shows the maximum absorbance at 255 nm in methanol solvent and the
linearity was observed in the concentration range of 2‐14 μg/ml and gave a mean correlation
coefficient 0.999. The excipients in the commercial tablet preparation did not interfere with
the assay. The developed UV Spectrophotometric method was found to be accurate, sensitive,
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
685
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
precise, and was successfully applied to a pharmaceutical tablet formulation for quantitative
estimation of Azelnidipine.
Selvadurai Muralidharan*, and co workers[8] have developed a simple, selective, rapid,
precise and economical reverse phase high pressure liquid chromatographic method(RP-
HPLC) has been developed for the estimation of Azelnidipine from pharmaceutical Tablet
dosage form. The method was carried out on a C18 (250 mm x 4.6 mm i.d., 5 µ) column with
a mobile phase consisting of acetonitrile: 0.5% triethyl amine (adjusted to pH 3.5 using
orthophosphoric acid) (70:30 v/v) at a flow rate of 1.0 ml/min. HPLC chromatographic
separation was performed on a Shimadzu liquid chromatographic system equipped with a
LC-20AD solvent delivery system (pump), SPD20A photo diode array detector, and SIL-
20ACHT injector with 50μL loop volume. LC solution version 1.25 was applied for data
collecting and processing. Detection was carried out at 254 nm. The retention time of
Azelnidipine was 4.9 min. The developed method was validated in terms of accuracy,
precision, linearity, limit of detection, limit of quantitation and solution stability. The
proposed method can be used for the routine analysis.
Megha G. Gore[9] et al have developed a simple and precise RP-HPLC method was
developed for the assay of azelnidipine from tablet formulation. The solvent system and
wavelength were optimized in order to maximize the sensitivity of the proposed method,
azelnidipine shows the maximum absorbance at 257 nm. The separation was achieved on
HPLC binary gradient system equipped with HPLC 3000 series. The mobile phase was
prepared with Methanol: Water (80: 20%v/v) o-phosphoric acid used for the pH adjustment
(pH-3). The method was validated for accuracy, precision, linearity, LOD & LOQ of sample
solution. Linearity was observed in the concentration range of 20-100 µg/ml & gave mean
correlation coefficient 0.998. The developed RP-HPLC method was found to be accurate,
precise and was successful applied to a pharmaceutical tablet formulation for qualitative
estimation of Azelnidipine.
Raveendra Babu Ganduri and coworkers[10] have developed a stability indicating RP-
HPLC method for the simultaneous determination of olmesartan medoxomil (OLM) and
azelnidipine from combined tablet dosage form. The separation was accomplished on Inertsil
3V (4.6 mm X 100 mm; particle size 3 µm) column using a mobile phase consisting of
potassium dihydrogen phosphate buffer (pH adjusted to 3.0 with orthophosphoric acid) and
acetonitrile in gradient elution mode. The analytes were monitored by a photo diode array
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
686
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
(PDA) detector set at 255 nm and the flow rate was kept at 2.0 mL min-1. The retention time
for olmesartan medoxomil and azelnidipine were 3.148 and 3.704 respectively. Linearity was
observed in the concentration range of 10-60 µg/mL for olmesartan medoxomil and 4-24
µg/mL azelnidipine. Both the drugs were subjected to acid, alkali and neutral hydrolysis,
oxidation, dry heat and photolytic degradation. The degradants were well resolved from the
pure drugs. The method could be used for simultaneous determination of olmesartan
medoxomil and azelnidipine in bulk and combined dosage form.
D. Prabhakar[11] et al., reported a simple, precise, accurate and sensitive reverse phase liquid
chromatographic method for the estimation of azelnidipine in the plasma of rat animal model
studies for transdermal drug delivery. The chromatographic method was standardized for
azelnidipine using Shimadzu HPLC model reverse phase analytical inspire C18 column (250
mm x 4.5 mm, 5 μm particle size) with LC10AD pump and SPD-10A UVDetector, The
mobile phase consists of75:25 methanol: waterand 0.1%glacial acetic acid, wave length at
254nm, with flow rate of 1ml/min. The retention time of azelnidipine found to be 6.130 min.
The method was statistically validated and %RSD was found to be less than 2 indicating high
degree of accuracy and precision. Hence this is proposed method can be successfully applied
for the estimation of azelnidipine in various dosage forms and animal model in –vivostudies.
RP-HPLC.
Jian – jun zou[12] et al., A simple, rapid and sensitive high performance liquid
chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) assay for
determination of azelnidipine in human plasma using perospirone as the internal standard (IS)
was established. After adjustment to a basic pH with sodium hydroxide solution, plasma
samples were extracted with diethyl ether and separated on a C18 column with a mobile
phase of methanol-5 mM ammonium acetate solution (90:10, v/v). The lower limit of
quantification (LLOQ) was 0.20 ng/ml. After administration of a single dose of azelnidipine
8mg and 16 mg, respectively; the area under the plasma concentration versus time curve from
time 0 h to 96 h (AUC(0-96) were (186 +/- 47) ng ml(-1) h, (429 +/- 145) ng ml(-1) h,
respectively; clearance rate (CL/F) were (45.94 +/- 11.61), (42.11 +/- 14.23) L/h,
respectively; peak plasma concentration Cmax were (8.66 +/- 1.15), (19.17 +/- 4.13) ng/ml,
respectively; apparent volume of distribution (Vd) were (1749 +/- 964), (2480 +/- 2212) L,
respectively; time to Cmax (Tmax) were (2.8 +/- 1.2), (3.0 +/- 0.9) h, respectively;
elimination half-life (t(1/2beta)) were (22.8 +/- 2.4), (23.5 +/- 4.2) h, respectively; and MRT
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
687
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
were (25.7 +/- 1.3), (26.2 +/- 2.2) h, respectively; The essential pharmacokinetic parameters
after oral multiple doses (8 mg, q.d.) were as follows: (Cmax) ss, (15.04 +/- 2.27) ng/ml;
(Tmax) ss, (2.38 +/- 0.92) h; (Cmin) ss, (3.83 +/- 0.94) ng/ml; C(av), (7.05 +/- 1.54) ng/ml;
DF, (1.62 +/- 0.26); AUCss, (169.19 +/- 36.87) ng ml(-1) h.
Yanhui Gao[13] et al., A robust and sensitive high-performance liquid chromatographic-
tandem mass spectrometric (HPLC-MS/MS) assay for the high-throughput quantification of
the antihypertensive drug azelnidipine in human plasma was developed and validated
following bioanalytical validation guidelines. Azelnidipine and internal standard (IS),
telmisartan, were extracted from human plasma by precipitation protein and separated on a
C18 column using acetonitrile-methanol-ammonium formate with 0.1% formic acid as
mobile phase. Detection was performed on a turbo-spray ionization source (ESI) and mass
spectrometric positive multiple reaction monitoring mode (+MRM) using the respective
transitions m/z 583.3 → 167.2 for azelnidipine and m/z 515.3 → 497.2 for IS. The method
has a wide analytical measuring range from 0.0125 to 25 ng/mL. For the lowest limit of
quantitation, low, medium and high quality controls, intra- and interassay precisions (relative
standard deviation) were 3.30-7.01% and 1.78-8.09%, respectively. The drug was sufficiently
stable under all relevant analytical conditions. The main metabolite of azelnidipine, M-1
(aromatized form), was monitored semiquantitatively using the typical transition m/z 581.3
→ 167.2. Finally, the method was successfully applied to a clinical pharmacokinetic study in
human after a single oral administration of azelnidipine 8 mg. The assay meets criteria for the
analysis of samples from large research trials.
Jenisha Modi[14] et al., have developed a Simple Estimated critical Spectrophotometric
methods was developed according to Quality by design (QbD) approach as per ICH Q8 (R2)
guidelines for estimation of Azelnidipine. QbD approach was carried out by varying various
parameters and these variable parameters was designed into Ishikawa diagram. The critical
parameters was determined by using principle component analysis as well as by observation.
RP-HPLC method was developed for estimation of AZEL utilizing isocratic separation mode
with Enable C18 (250×4.6mm.; 5 micron) column, optimum mobile phase consist of Sodium
diabasic Phosphate Buffer: Acetonitrile: Methanol in the ratio of (10:50:40 v/v/v) ph adjust
4.50 by o-phosphoric acid. With effluent flow rate of 1ml/min and detecting wavelength at
257 nm in UV detector. parameters in zero order Spectrophotometric method were solvent
(methanol + water), sample preparation API, Wavelength 257nm. And for first order
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
688
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
derivative Spectrophotometric method it was sacling factor: 10 and delta lambda 4. The
validation of the proposed method was found to be in compliance with the ICH guideline. For
HPLC method the linearity was observed in concentration range of 2-10μg/ml for AZEL. The
validation of the proposed method was found to be in compliance with the ICH guideline.
The developed HPLC method was subjected to stability indicating studies for bulk
formulation. Interfering peak from degraded products or solvent did not interfere with
estimation of drug and the developed method was found to be specific for estimation of
Azelnidipine.
Suneetha G[15] et al., specifies the method for analysis of azelnidipine in human plasma by
ultra-performance liquid chromatography tandem mass spectrometry. azelnidipine was
analyzed by the system with a C18 column. The linearity of calibration curve in the range of
0.01 - 10 ng/ml or quality control samples spiked with azelnidipine. The detection limit was
as low as 1 pg/ml.
Rele RV[16] et al., specifies UV- spectrophotometric methods, first order derivative and area
under curve [AUC], have been developed and validated for the estimation of Azelnidipine in
bulk drug and its tablet formulation. The methanol is used as a solvent. It was estimated at
242.6 nm for the first order derivative UV-spectrophotometric method (A) while in area
under curve (AUC) method (B) the zero order spectrum of Azelnidipine was measured in
between 250.5 nm to 258.8 nm. Beer’s law was obeyed in the concentration range of 1 to 20
μg/ml. Similarly in AUC method, Beer’s law was obeyed in the concentration range of 1 to
20 μg/ml with coefficient of correlation value 0.9991.
Rele RV[17], specifies second order derivative have been developed and validated for the
estimation of Azelnidipine in bulk drug and its tablet formulation. The methanol was used as
a solvent. It was estimated at 233.8 nm for the second order derivative UV-
spectrophotometric method. Beer’s law was obeyed in the concentration range of 1 to 20
µg/ml with coefficient of correlation value 0.9993.
Amin AA.[18], et al. specifies the RP-UFLC method for simultaneous determination of
azelnidipine and olmesartan medoxomil in Pharmaceutical Dosage form. The
chromatographic separation was achieved by using Phenomenex, Prodigy, ODS3, 5 µm, 100
Å, (250 x 4.6 mm) analytical column with a mobile phase consisting of methanol and water at
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
689
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
the ratio of (85:15% v/v). The flow rate was set at a 1.5 ml/min, and detector wavelength of
255 nm using a PDA detector.
Rane AS[19] et al., specifies the stability indicating HPTLC method for the estimation of
Azelnidipine on the plates precoated with silica gel 60 F254. The mobile phase used was
Chloroform: Ethyl Acetate: Methanol in the ratio of 6.5:3.5:0.1 v/v/v. The drug showed
absorbance maxima at 255 nm. The data of linearity indicated a good linear relationship over
the range of 300 - 800 ng/band concentrations.
Gore MG[20] et al. specifies the a simple method for the assay of azelnidipine from tablet
formulation. Azelnidipine shows the maximum absorbance at 257 nm Chromatographic
separation was performed on a reverse phase Hexon C8 shield The mobile phase was a
mixture of methanol and water (80:20% (v/v)). The flow rate was adjusted to 1.0 ml/min.
Linearity was observed in the concentration range of 20 - 100 µg/ml.
Patel NK[21] et al. specifies a RP-HPLC method for the simultaneous determination of
Azelnidipine (AZL) and Olmesartan (OLM). The chromatographic separation was achieved
using a Hypersil GOLD C18 (150 mm × 4.6 mm internal diameter, 5 µm particle size)column
with a mobile phase composed of methanol, acetonitrile, and water in the ratio of 40:40:20
(v/v/v). The flow rate was set at a 0.5 ml/min, and quantification of the analytes was based on
measuring their peak areas at 260 nm. The retention times for Azelnidipine and Olmesartan
were about 8.56 and 3.04 min, respectively. The linearity was observed in the ranges of 2 - 48
μg/ml for Azelnidipine and 2.5 - 60 μg/ml for Olmesartan.
Patel N.[22] et al. specifies the First Derivative Spectrophotometric method for the
simultaneous estimation of Azelnidipine and Olmesartan medoxomil in synthetic mixture.
Quantitative determination of the drugs was performed at 239.4 nm and at 217 nm for
Azelnidipine and Olmesartan medoxomil, respectively. Quantification was achieved over the
concentration range of 4 - 32 µg/ml for Azelnidipine and Olmesartan medoxomil disoproxil
fumarate. The AR grade methanol is used as a solvent.
DISCUSSION
The presented review highlights on various analytical methods reported for estimation of
Azelnidipine in alone or in combination with Olmesartan medoxomil in marketed
formulation and biological matrix like human plasma. RP-HPLC and UV methods were
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
690
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
found to be most widely used methods. These methods are found to be rapid, accurate,
sensitive, economical and reproducible for determination of Azelnidipine in various marketed
formulations and biological matrix.
CONCLUSION
So, from all above information it should be concluded that various spectroscopic methods,
chromatographic methods and other methods were used for determination of Azelnidipine
alone or in combination which has been successfully used on a routine basis and allows the
quantification of the drug in various pharmaceutical dosage form and in biological matrix in
short analytical time.
REFERENCES
1. Walker R and Whittlesea C. Clinical Pharmacy and Therapeutics; 5th Edn; Elsevier, 2007;
295-307.
2. Shewale VU, et al., Azelnidipine: A Review on Therapeutic Role in Hypertension.
Journal of Drug Delivery and Therapeutics, 2019; 9: 1002-1005.
3. Chen B et al, Clinical use of azelnidipine in the treatment of hypertension in Chinese
patients”. Therapeutics and Clinical Risk Management, 2015; 11: 309-318.
4. Drug profile of Azelnidipine, 2019.
5. “Azelnidipine”, 2019.
6. Tamargo J and Ruilope LM.,Investigational calcium channel blockers for the treatment of
hypertension, Expert Opinion on Investigational Drug, 2016; 1-51.
7. Raskapur KD, et al., UV-Spectrophotometric Method Development and Validation for
Determinaton Of Azelnidipine In Pharmaceutical Dosage Form, International Journal of
Pharmacy and Pharmaceutical Sciences, 2011; 238-240.
8. Muralidharan S, S. Parasuraman and V. Venugopal, Simple Validation of Azelnidipine
By RP-HPLC Method, Rapports De Pharmacie, 2015; 1(1): 43-45.
9. Gore MG and Dabhade PS, RP-HPLC Method Development and Validation of
Azelnidipine, IJPSR, 2016; 5111-5114.
10. Raveendra Babu Ganduri, Jayachandra Reddy Peddapapireddigari, Himabindu Vurimindi
and Rampraksah, stability indicating liquid chromatographic method for the simultaneous
determination of olmesartan medoxomil and azelnidipine in combined tablet dosage form
International Journal of Pharma Sciences and Research (IJPSR), 2014; 5: 275-282.
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
691
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
11. Prabhakar D, Sreekanth J, Jayaveera K.N., Method Development and Validation of
Azelnidipine by RP-HPLC, International Journal of ChemTech Research, 2017; 10:
418-423.
12. Jian – jun zou, Hong-jian ji, Xiao-Hua Zhou, Yu-Bin Zhu, Hong –wei Fan, Da-Wei Xiao,
Qin Hu, Determination of azelnidipine by LC-ESI-MS and its application to a
pharmacokinetic study in healthy Chinese volunteers, Pharmazie, 2008; 63(8): 568-70.
13. Yanhui Gao,Baoqiu Li, Baomeng Zhu, Hengli Zhao, Zengjun Fang, Haisheng Wang,
Hongxiang Lou, A liquid chromatography–tandem mass spectrometric assay for the
antihypertensive agent azelnidipine in human plasma with application to clinical
pharmacokinetics studies,Wiley Online library,Biomedical chromatography, 2014; 29(7):
970-974.
14. Jenisha M, Shivangi P, Namrata P, Shreya S, Prasanna P and U. M. Upadhyay, stability
indicating analytical method development and validation for estimation of azelnidipine,
World Journal of Pharmaceutical Research, 2016; 5(2): 831-847.
15. Suneetha G.,, P. Venkateswarlu and P.S.S. Prasad Sensitive Analysis of Azelnidipine and
Related Derivative in Human Plasma by Ultra-Performance Liquid Chromatography-
Tandam Mass Spectrometry, Asian Journal of Chemistry,2013;25(18) : 10319-10321.
16. Rele RV, Spectrophotometric Estimation of Azelnidipine in Bulk drug and
Pharmaceutical Dosage form by First Order Derivative and Area Under Curve Methods,
American Journal of PharmTech Research, 2014; 4(2): 126-135.
17. Rele RV Spectrophotometric estimation of azelnidipine in bulk and pharmaceutical
dosage form by second order derivative method, Journal of Chemical and Pharmaceutical
Research, 2014; 6(8): 198-202.
18. Amin AA,Saad M and Ahmed M, Simultaneous Determination of Azelnidipine and
Olmesartan Medoxomil in Pharmaceutical Dosage Forms by UFLC Method, Journal of
Pharma SciTech, 2016; 69-74.
19. Rane AS and Mahajan SK, Validation and Forced Stability Indicating HPTLC Method
for Determination of Azelnidipine, World Journal of Pharmaceutical Research, 2016;
1053-1056.
20. Gore MG and Dabhade PS, RP-HPLC Method Development and Validation of
Azelnidipine, IJPSR, 2016; 5111-5114.
21. Patel NK and Patel JK, Validated Stability-Indicating RP-HPLC Method for the
Simultaneous Determination of Azelnidipine and Olmesartan in Their Combined Dosage
Form, Scientia Pharmaceutica, 2014; 82: 541-554.
www.wjpps.com │ Vol 10, Issue 3, 2021. │ ISO 9001:2015 Certified Journal │
692
Mandale et al. World Journal of Pharmacy and Pharmaceutical Sciences
22. Patel N and Patel JK, Simultaneous Determination of Azelnidipine and Olmesartan
medoxomil, by First Derivative Spectrophotometric Method, Scholar Research Library,
2012; 4(4): 1080-1084.
