Analytical Methods for the Estimation of Ranolazine in Bulk and
Dosage Forms: A Comprehensive Review
Patlolla Pravalika*, Mamindla Ravali, Endulal Akash, Mudavath
Sindhu, Tadikonda Rama Rao
CMR College of Pharmacy,
Kandlakoya, Medchal, Hyderabad, Telangana,India-501401
*Correspondence: pravalika.jntu@gmail.com Contact no: 9963100541
DOI: https://doi.org/10.71431/IJRPAS.2025.4604
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Article
Information
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Abstract
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Research Article
Received: 20/06/2025
Accepted: 25/06/2025
Published: 30/06/2025
Keywords
Ranolazine;
Anti-ischemic;
Angina;
HPLC; HPTLC.
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A novel anti-ischemic medication for the treatment of angina is
ranolazine, a derivative of piperazine. The function of ranolazine is to
suppress late INa, hence avoiding cell sodium overload. Ranolazine thereby
inhibits reverse mode sodium-calcium exchange, which in turn inhibits the
diastolic buildup of calcium. This may lead to an improvement in diastolic
tone and coronary blood flow. Myocardial ischaemia is treated with
ranolazine, which affects sodium-dependent calcium channels.
This review article
represents the various analytical methods which has been reported for estimation
of Ranolazine in bulk drug and its dosage forms. The spectrophotometric
techniques like UV, Visible and fluorescence spectroscopy; Chromatographic
methods like HPLC, HPTLC and RP HPLC, GC, LC-MS, LC-MS/MS were reported.
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INTRODUCTION
Ranolazine
is a chemical derivative of apiperazine and is used as an antianginal
medication. Its structural formula is
N-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy) propyl]1-yl
piperazine] acetamide shown in fig no:1.It dissolves readily in methanol. The
six-membered piperazine ring in ranolazine gives it a strong base with a pKa
value of 13.6. Ranolazine has a melting point of 122-124 °C. [1] Ranolazine is thought to decrease calcium
uptake indirectly through the sodium/calcium exchanger because it lowers the
late sodium current and is anticipated to decrease sodium entry into ischemic
myocardial cells. It also has antianginal and anti-ischemic effects that are
independent of drops in blood pressure or heart rate.
For
patients who have not responded well to other antianginal medications, the
medication may be administered in combination with them. In the US,
extended-release ranolazine was just authorized for the management of
persistent angina.[2]
Ranolazine
is available in dosage forms, including tablets, film-coated and
extended-release tablets. It is advised to take 500–1000 mg of ranolazine twice
day. [3]
Fig no:1 Structure of Ranolazine
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Mechanism
of action:
The
anti-anginal and anti-ischemic actions of ranolazine have an unclear mechanism.
The late phase of inward sodium channels in ischemic cardiac myocytes is known
to be inhibited by ranolazine, which lowers intracellular sodium concentration
and, consequently, intracellular calcium influx through the Na-Ca channel.Shown
in Fig no:02. While it has no effect on heart rate or blood pressure, decreased
intracellular calcium lowers ventricular wall strain and, consequently, oxygen
consumption. In 191 patients with activity-limiting angina, the Monotherapy Assessment
of Ranolazine in Stable Angina (MARISA) trial randomized them to receive 500
mg, 1000 mg, or 1500 mg twice day, or a placebo, for a duration of one week.
Compared to a placebo, ranolazine considerably extended the duration of
exercise while having no effect on blood pressure or heart rate.
The
action potential is delayed and the QT interval is prolonged at larger
concentrations of ranolazine because it inhibits rapid delayed rectifier
potassium current. Ranolazine also prevents the oxidation of fatty acids, which
increases the oxidation of glucose, decreases the generation of lactic acid,
and strengthens the heart.[4]
Fig no:02 Mechanism of Ischaemia
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Pharmacology:
Pharmacodynamics
Ranolazine
blocks potassium and sodium ion channel currents at clinically therapeutic
levels.[5] During cardiac repolarization, inhibition of the late phase of the
inward sodium current has been thoroughly investigated. Increase in the late
phase of the inward sodium current activity cause higher sodium–calcium
exchange in illness situations, which raises the concentration of calcium in
the cytosol.[6] The process by which ischemia and reperfusion reduce left
ventricular relaxation is thought to be significantly influenced by intracellular
calcium excess.[7]
The
myocardial blood flow is further compromised by elevated diastolic wall tension
in the left ventricle. Furthermore, myocardial electrical activity is
negatively impacted by calcium excess, which increases the risk of ventricular
tachycardia. Although this mechanism has been well examined, mostly in rats,
there is insufficient evidence to support the anti-ischemic action of
ranolazine in patients with ischemic heart disease, which is caused by late Na
channel blockage increasing myocardial perfection.[8]
Pharmacokinetics
Absorption:
The steady-state concentration of ranolazine is reached in 3 days, with a peak
concentration occurring in 2–6 hours.
Distribution:
The steady-state volume of distribution
for ranolazine is between 85 and 180 L.[5]
Metabolism:
CYP3A4 enzymatic activity is the primary catalyst for the drug's fast
hepatocellular metabolism; CYP2D6 plays a minor role. There are more than 100
distinct ranolazine metabolites known to exist in urine, and more than 40 in
plasma.
Elimination:
About 75% of the dose is eliminated
through the kidneys, with the remaining portion being eliminated through the
stool. The half-life of the medication is roughly seven hours.[4]
Clinical
research in angina with ranolazine:
Compared
to comparison arms, ranolazine, either alone or in combination with other
antianginal medications, has been demonstrated in several randomised controlled
trials to minimise angina events, improve exercise tolerance, and,
consequently, lower the frequency of nitroglycerin use.
participants with stable angina were recruited for the Monotherapy Assessment
of Ranolazine in Stable Angina (MARISA) research, a double-blind randomised
controlled study. 191 participants were given ranolazine at various doses (500,
1000, …) [9]
Ranolazine
and incomplete revascularization after percutaneous coronary intervention
The
RIVER-PCI trial assessed the use of ranolazine in individuals who had undergone
percutaneous coronary intervention (PCI). 2651 participants with a history of
stable angina and inadequate revascularisation participated in this
double-blind, randomised study.[10] The time to first ischemic-driven
revascularisation or hospitalisation without revascularisation was the main
outcome measure. Between ranolazine and placebo, there was no difference (26%
vs. 28%, p = 0.48).[11
Ranolazine
in acute coronary syndrome:
Patients
with non-ST-elevation acute coronary syndrome were assessed under ranolazine
medication in the MERLIN-TIMI 36 trial. This trial included 6560 individuals
who experienced ischaemic symptoms within 48 hours. It was randomised,
double-blind, and placebo-controlled. 3281 matched patients received a placebo,
while 3279 individuals received ranolazine (intravenously, then 1000 mg orally
b.i.d.). Death, myocardial infarction, or recurrent ischaemia combined was the
main outcome.[12].
Clinical
research in microvascular angina with ranolazine:
Ranolazine
or a placebo was randomly assigned to 81 individuals with microvascular angina
in a double-blind, randomised cross-over study. Using magnetic resonance
imaging (MRI), the left ventricular volume and myocardial perfusion reserve
index (MPRI) were measured. Symptomatic patients with coronary flow reserve
(CFR) <2.5 and no obstructive epicardial coronary heart disease showed
improved myocardial perfusion and decreased angina with ranolazine.[13].
Diabetes:
Many
people with angina symptoms have many comorbidities, and a sizable fraction of
them have diabetes mellitus. Of the 1957 people with CAD analysed in the National
Health and Nutrition Examination Survey (NHANES) cohort, 48.9% of the DM
patients also experienced angina symptoms. For these patients, it is therefore
preferable to utilise an antianginal medication that improves their glycaemic
profile.[14].
Dosage
Forms:
Ranolazine
is available as tablets, film-coated and extended-release tablets
Dose: 500 mg and 1000
mg.
Adult
Dosing:
The
recommended starting dosage is 500 mg twice a day, which can be increased to
1000 mg twice a day as tolerated. 1000 mg twice daily is the highest dosage
that is advised. Because the tablets are film-coated and not scored, they
shouldn't be chewed, broken, or crushed. Ranolazine can be given regardless of
meals because food has no effect on the absorption rate or the area under the
plasma concentration-time curve (AUC). The half-life is 7 hours, the steady
state concentration is obtained in 3 days, and peak plasma concentrations are
reached between 2 and 5 hours [15].
When
taking moderate CYP3A inhibitors such as erythromycin, verapamil, and diltiazem
with ranolazine, a dose adjustment is necessary. No more than 500 mg should be
taken twice daily. Since P-glycoprotein inhibitors (like cyclosporine) may also
raise ranolazine plasma concentrations, dosage should be adjusted based on clinical
response for individuals receiving both medications concurrently [16].
Adverse
Effects:
The
most frequent side effects included headaches, nausea, vertigo, tinnitus,
dizziness, blurred vision, palpitations, anorexia, vomiting, anorexia,
dyspepsia, peripheral edema, and constipation. Thrombocytopenia, leukopenia,
angioedema, renal failure, eosinophilia, pulmonary fibrosis, syncope,
hematuria, bradycardia, hypotension, orthostatic hypotension, and pancytopenia
are among the more serious side effects. Although a small number of
ranolazine-induced myopathy instances have been documented, these are extremely
uncommon, and the prognosis for these individuals is favorable after stopping
the medication.
Postmarketing
side effects include dermatitis, dysuria, paresthesia, tremors, hallucinations,
and aberrant coordination. Usually dose-dependent, reported neurologic effects
go away when the medication is stopped[17].
Drug-Drug
Interactions:
Enzymes
CYP3A4 and, to a lesser extent, CYP2D6 are responsible for the liver's primary
metabolism of ranolazine. P-glycoprotein also takes up ranolazine as a
substrate. It is not recommended to use strong CYP3A4 inhibitors such as
ritonavir, clarithromycin, and ketoconazole concurrently since they raise
ranolazine levels. Ranolazine levels rise in response to moderate CYP3A4
inhibitors, including verapamil, erythromycin, fluconazole, and diltiazem. The
dosage of ranolazine should not be more than 500 mg twice a day when taken
concurrently; careful observation is necessary. It is not advised to take
ranolazine concurrently with CYP3A4 inducers including rifampin, carbamazepine,
phenytoin, and St. John's wort since they lower ranolazine plasma levels.
Patients with cirrhosis of the liver should not use this medication, however there
are no suggested dose changes for those with hepatic impairment.[7]
Metformin
plasma concentrations were raised when ranolazine and metformin were
administered together at a dose of 1000 mg twice daily. Patients using 1000 mg
of ranolazine twice a day should not take more than 1700 mg of metformin per
day, and their blood sugar levels should be regularly checked.[9]
Toxicity:
Hallucinations,
nausea, vomiting, tremors, dizziness, and dysphagia can all increase in
dose-dependent ways while taking high doses of ranolazine. In overdose
situations, supportive therapy ought to be administered. An overdose of
ranolazine may necessitate ECG monitoring. Due to the approximately 62% binding
of ranolazine to plasma proteins, haemodialysis is insufficient for an overdose.[18].
Overview
of Analytical methods for determination of Ranolazine in Biological and
Pharmaceutical samples
The
distribution of typical analytical techniques for ranolazine is shown in this
pie chart. The most common techniques in research with ranolazine, such as mass
spectrometry, UV-visible spectroscopy, and HPLC, were shown in the chart Fig
no:03.
HPLC
(High pressure liquid chromatography)40%
LC-MS
/ LC-MS/MS (Liquid Chromatography-Mass Spectrometry) 25%
UV-Visible
Spectrophotometry 15%
UPLC (Ultra-Performance Liquid Chromatography) 10%
Stability-Indicating
Methods (Forced Degradation Studies) 5%
Electrochemical
Methods (e.g., Voltammetry) 3%
Other Methods
(e.g., TLC, Capillary Electrophoresis) 2%
Fig no: 03
Analytical methods of Ranolazine
I. Chromatographic
Methods:
Ranolazine
is mostly estimated using high-pressure liquid chromatography (HPLC). It can
also be determined using the GC technique. One popular chromatographic
technique for analysing ranolazine in formulation is HPTLC. Hyphenated
techniques like LC-MS/MS, LC-MS and UHPLC were also used to estimate the amount
of ranolazine in biological fluids like plasma. The RP HPLC method was also
created to measure the amount of ranolazine in human serum are shown in Table
no.1.
Table
No.1: Chromatographic Method of Ranolazine
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Title
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Method
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Mobile phase
|
Stationary phase
|
Wave Length
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Reference
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Ranolazine in
bulk and marketed formulation
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HPLC
and UV
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Methanol:
0.5% tri ethyl amine,pH6 with orthophosphoric acid (75:25)
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-
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271
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8
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Estimation
of Ranolazine HCL in Tablet Dosage Form
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RP-HPLC
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Buffer: Acetonitrile(60:40)pH
adjust with triethylamine
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Inertsil ODS
C18
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224
nm
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9
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Determining
Related Substances in Compatibility Studies in novel Formulation for Ranolazine.
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HPLC
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Phosphate
buffer pH 7.0: methanol (350:650 v/v)
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Supelcosil C18 column
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220
nm
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10
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Estimation
of Ranolazine in tablet dosage form
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RP-HPLC
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Sodium dihydrogen phosphate
buffer (pH adjust to 5 with dilute orthophosphoric acid): Acetonitrile (600:400)
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X-terra
C18 column
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210
nm
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11
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|
Estimation
of Ranolazine in Bulk and Tablet Dosage Form
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RP-HPLC
|
Ammonium
acetate buffer pH-4: Acetonitrile: Methanol(30:50:20)
|
ODS
C18 column
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200
nm
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12
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|
Estimation
of Ranolazine in bulk and Pharmceutical formulation
|
RP-HPLC
|
Sodium dihydrogen phosphate
buffer pH adjust to 5 with
dilute orthophosphoric acid: Acetonitrile (600:400)
|
X-terra
RP18 column
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225
nm
|
13
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|
Determination
of Related Component and Assay of Ranolazine
|
LC
|
-
|
C18 column
|
210
nm
|
14
|
|
Determination
of Ranolazine HCL in bulk and dosage form
|
LC
|
Methanol:
water (99:1 %,V/V)
|
HiQ Sil C18 HS
|
273
nm
|
15
|
|
Quantitation of Ranolazine in
rat plasma
|
LC
|
-
|
C18 column
|
-
|
16
|
|
Quantitation of Ranolazine in
rat plasma
|
LC
|
Acetonitrile:
water: formic acid: 10% n-butylamine (70:30:0.5:0.08,
v/v/v/v)
|
Nova-Pak
C18 column
|
-
|
17
|
|
Determination
of Ranolazine in human plasma
|
HPLC
|
Acetonitrile:0.1%
formicacid(90∶10)
|
Agilent-ZORBAX C18 column
|
-
|
18
|
|
Estimation
of Ranolazine in Human Plasma
|
LC
|
Methanol–10mM
acetate (60:40 v/v, pH 4.0)
|
Zorbax extend C18 column
|
-
|
19
|
|
Ranolazine HCL
in bulk and tablet dosage form
|
HPTLC
|
Chloroform:methanol:
toluene (5 :1 : 1 v/v/v)
|
silica
gel aluminium plate 60 F – 254
|
273
nm
|
20
|
|
Estimation
of Ranolazine
|
HPTLC
|
Methanol : 10mM ammonium
acetate solution (6:4 V/V)
|
Aluminium plates precoated with
Silica gel G 60 F254
|
271
nm
|
21
|
|
Estimation
of Ranolazine
|
RPHPLC
|
Phosphate
buffer pH 3.5 : Acetonitrile 65:35 (v/v)
|
Agilent
Eclipse XDB C18 column
|
272
nm
|
22
|
|
Estimation
of Ranolazine and eleven phase I metabolites
|
LC-MS
|
-
|
Source- Finnigan MAT
TSQ 700 MS
|
-
|
23
|
|
Analysis
of Ranolazine and Dimethyl ranolazine
|
LC-MS/MS
|
-
|
Chiralcel ODH
Column
|
-
|
24
|
|
Quantitation of ranolazine in
human plasma
|
U-HPLC-MS/MS
|
Acetonitrile aqueousammoniumacetate
solution(40:60, V/V)
|
BEH C18 column
|
-
|
25
|
|
Quantitation of ranolazine and
its three metabolites
|
LC-MS/Ms
|
Methanol:
5 mM ammonium acetate
|
Gemini C18 column
|
-
|
26
|
|
Estimation
of Ranolazine in human plasma
|
LC-MS/MS
|
Methanolwater
containing formic acid (1.0%, v/v) (65:35, v/v)
|
Peerless Cyano column
|
-
|
27
|
|
Semi
preparative resolution of ranolazine enantiomers
|
LC
|
Methanol
|
Cellulose tris(3,5dimethylphenylcarbamate) Chiral stationary
phases
|
-
|
28
|
|
Method
for Ranolazine dihydrochloride and its degradation product
|
RPHPLC
|
Methanol: Acetonitrile :
phosphate buffer (pH 3.6,6.3 mM) (4 : 3 :3, V/V)
|
C18 column
|
220
nm
|
29
|
|
Estimation
of ranolazine in dog urine
|
LC-MS
|
-
|
-
|
-
|
30
|
|
Determination
of ranolazine in rat plasma
|
LC-MS
|
Methanol:10 mM ammonium
acetate (76 : 24 V/V)
|
C18 column
|
-
|
31
|
|
Determination
of Ranolazine drug substance and drug product
|
RP-UPLC
|
Monobasic
sodiumbuffer : acetonitrile
|
Acquity BEH
RP18
Column
|
-
|
32
|
|
Determination
of residual solvents in Ranolazine
|
GC
|
-
|
HP-INNOWAX
column
|
-
|
33
|
II. UV
spectroscopic method:
UV
spectroscopy techniques like First order derivative spectroscopy and Area Under
curve spectroscopic technique were developed for determination
of Ranolazine. Even Colorimetry and Visible spectroscopy method
was developed for estimation of Ranolazine are shown in Table no.2.
Table
No.2: UV spectroscopic method
|
Title
|
Method
|
Wavelength
|
Linearity and R2
|
Recovery
|
REF
|
|
Estimation
of Ranolazine in bulk drug and pharmaceutical formulation
|
UV
method
|
272
nm
|
10-100
µg/ml
|
99.77-100.33
%
|
34
|
|
Estimation
of Ranolazine in bulk and pharmaceutical dosage form
|
First
order derivative spectroscopic method
|
263
nm and 282 nm
|
10-35
µg/ml and 0.9992
|
-
|
35
|
|
Estimation
of ranolazine in API and tablet formulation
|
Area
under curve method
|
261nm
and 281 nm
|
75-200
µg/ml and 0.998
|
99.42-99.97
%
|
36
|
|
Estimation
of ranolazine in bulk and formulation
|
Novel
spectrometric method
|
272
nm
|
10
– 100 µg/ml
|
99.345-100.43
%
|
37
|
|
Estimation
of ranolazine in bulk
|
Nanodrop spectrometric
method
|
272
nm
|
12.5-2000
µg/ml
|
-
|
38
|
|
Development
for some amide group containing drugs using
Bougainvillea spectabilis bract extracts
|
Colorimetry
|
418
nm
|
5-25
µg/ml
|
-
|
39
|
|
Determinationofranolazinein
bulk and synthetic mixture
|
Colorimetry
|
731
nm
|
525
mg/ml
|
-
|
40
|
|
Estimation
of ranolazine in formulation
|
Visible
spectroscopy
|
510
and 525 nm
|
-
|
-
|
41
|
Table No.3:
RP HPLC Method for simultaneous estimation
of Ranolazine and Dronederone
|
Title
|
Method
|
Mobile phase
|
Stationary phase
|
Wave length
|
Ref.
|
|
Simultaneous
estimation of Ranolazine and Dronederone in bulk and
pharmaceutical dosage forms.
|
HPLC
|
0.02N
NH2PO4 buffer (pH4) Acetonitrile (50 :50 V/V)
|
ODS
column
|
282
nm
|
43
|
|
Simultaneous
estimation of Ranolazine and Dronederone in bulk
|
RPHPLC
|
Ammonium
acetate buffer(pH4): Acetonitrile (50 : 50 V/V)
|
X-terra
C18 column
|
275
nm
|
44
|
FTIR
Method (Fourier Transform Infrared Spectroscopy):
FTIR
measures the absorption of infrared light at various wavelengths to determine
the chemical functional groups present in ranolazine. The molecule's functional
group bonds and molecular vibrations are revealed by the infrared spectra.[18]
DSC
Method (Differential Scanning Calorimetry):
DSC
calculates the temperature-dependent heat flow linked to phase transitions in a
material. This method is frequently employed to investigate thermal
characteristics such as melting temperatures, compound degradation, and
crystallisation.[21]
CONCLUSION:
This
review aimed at focusing various analytical methods reported for the assay of
Ranolazine anddrug information like mechanism of action pharmacodynamics and
pharmacokinetics etc were discussed. A broad range of techniques are available
for the estimation of Ranolazine in biological samples and pharmaceutical
dosage forms. The analysis of published data revealed that spectrometric
methods are the simple and economical methods for estimation of Ranolazine in
pharmaceutical formulations. For analysis of Ranolazine, HPLC-UV, RP-HPLC, LC,
HPTLC, GC, provides accurate results and low cost compared to advanced
detection techniques. The presented information is useful for the future
study for researcher involved in formulation development and quality control
of Ranolazine
ACKNOWLEDGEMENT:
The
authors would like to sincerely thank CMR College of Pharmacy for providing the
supportand resources needed for this review. Our gratitude goes out to our
guide and friends for theirinsightful comments and helpful debates that
influenced the development of this paper.
REFERENCES :
1.
Patel Vishakha. D. Raj Hasumati, Gheewala
Nirav,A Review on Analytical Methods for Ranolazine determination in synthetic
mixture; Pharma Tutor; 2016; 4(4); 28-31
2.
Priyanka Patil, Shyam Rangari, Priya
Patil, Research on analytical methods of analysis of Ranolazine: A Review,
Himalayan Journal of Health Sciences; 2020; 5(4);30-40.
3.
Zubaidur
Rahman, MohidulIslam, Moidul Islam Judder, Sadiqul Alam1,Moksood Ahmed Laskar, A
Review on Analytical Development and Determination Method of Ranolazine in
synthetic mixture; Indian Journal of Research in Pharmacy and Biotechnology
(IJRPB);2022;10 (1);18-27.
4.
Vivek
Nalawade, Parag Gide, Govind Nunnavare, Mitesh Phale, Development and
Validation of RP-HPLCMethod for the Determination of Ranolazine in Human
Plasma,International Journal of Pharmaceutical Sciences;2010;2(1):369-374.
5.
Erin Rayner‐Hartley , Tara Sedlak, Ranolazine: A Contemporary Review, National library of
medicine;2016;15;5(3);1-8.
6.
Reddy BM,
Weintraub HS, Schwartzbard AZ. Ranolazine: a new approach to treating an old
problem. Tex Heart Inst J. 2010;37(6):641-7.
7.
Al Batran R,
Gopal K, Aburasayn H, Eshreif A, Almutairi M, Greenwell AA, Campbell SA, Saleme
B, Court EA, Eaton F, Light PE, Sutendra G, Ussher JR. The antianginal
ranolazine mitigates obesity-induced nonalcoholic fatty liver disease and
increases hepatic pyruvate dehydrogenase activity. JCI Insight. 2019
Jan 10;4(1).
8.
Parvatha
reddy S, Desam N, Nuthalapati M, B.T, Development and
Validation of HPLC and UV methods for estimation
of Ranolazine in Bulk and Marketed formulation , International
journal of Innovative Pharmaceutical Sciences and Research, 2014, 2(5),
1042-1058
9.
Patel
R.C, Rathod D.K, Patel P.R, Patel V.S, Estimation
of Ranolazine Hydrochloride by Spectrophotometric and RP-HPLC in
tablet dosage forms., International Journal of Pharmaceutical
and Applied Sciences, 2010, 1(2), 79-83
10.
VV.S,
V.S, Tegk.M, Validated HPLC method for Determining Related Substances in
Compatibility studies and Novel extended release formulation
for Ranolazine, J. Chromatography Separation Techniques, 2014, 5(1), 1-7
11.
G.L,
K.H, Agarwal N, Development and validation of stability indicating
RP-HPLC method for estimation of Ranolazine in bulk and tablet dosage
form. , International Research Journal of Pharmaceutical and Applied Sciences,
2012, 2(5), 217-223
12. Soujanya A, K.V.S, Puttagunta S, Method Development and
Validation for estimation of Ranolazine in its bulk and tablet dosage
form., International Journal of inventions in Pharmaceutical Sciences, 2013,
1(4), 363-369
13. Ganji R, D. R, G. S, Jayapal G, P.
R, Srilakshmi V, Development and Validation of stability indicating
RP-LC method for estimation of Ranolazine in bulk and its
Pharmaceutical formulation., American Journal of analytical Chemistry, 2012, 3,
378-384
14. A.M, Venkata S.D, P.S, A.N, Development and Validation of a
new analytical method for the Determination of related components and assay
of Ranolazine in bulk drug and pharmaceutical dosage forms by LC.,
J. Chromatographia, 2009, 70(1), 333-338
15. Sharma T, Moitra S.K, Si.S.C, Sankar D.G,
Stability indicating LC method for the determination
of Ranolazine Hydrochloride in the bulk drug and in pharmaceutical
dosage form. International Journal of Pharmacy and Pharmaceutical Sciences, 2011,
3(4), 327-332
16. Liang Y, Xie L, Liu XD, Chen WD, Lu
T, Xiong Y, Wang Gj, Simple, sensitive and rapid liquid
chromatography/atmospheric pressure chemical ionization mass spectrometric
method for the quantitation of Ranolazine in rat plasma.,
Rapid Commun Mass Spectrum, 2006, 20(4), 523-528
17. Lei T, Juanjuan J, Yiling H, Lu H, Hong
L, Yishi L, Sensitive quantification of Ranolazine in human
plasma by liquid chromatography-tandem mass spectrometry with
positive electrospray ionization., Journal of Chromatography B, 2007,
846(1-2), 346-350
18. Bai S, Gao H, Qu H, Liang Y, Li
Y, Zheng Z, Wang X, Hao G, Quantitative determination
of Ranolazine in human plasma by high performance liquid
chromatography-tandem mass spectrometry.Northwest Pharmaceutical Journal, 2011
19. Zhao L, Li H, Jiang Y, Piao R, Li P, Gu J
,Determination of Ranolazine in human plasma by liquid
chromatographic-tandem Mass Spectrometric assay, journal of Chromatographic
Science, 2008, 46(8), 697-700
20. Khedkar A.N, Veer S.U, Rakh M.S, Rao J.R,
Stability indicating method development and validation of
Ranolazine Hydrochloride in bulk and tablet dosage form by
HPTLC International Journal of
Pharmaceutical and Clinical Research, 2015, 7(1), 77-83
21. Chakraborty R, Pal K, Shaiba M, Sangepu N, P.S,
High performance thin layer
chromatographic,,estimation,of Ranolazine. Researh journal of
Pharmaceutical, Biological and Chemical Sciences, 2010, 1(4), 152-157
22. Boovizhikannan T, Palanirajan V, Estimation
of Ranolazine using Reverse phase High Performance liquid Chromatography
Technique., American journal of Pharma Tech Research, 2012, 2(6),
23. Herron W.J, Eadie J, Penman A.D, Estimation
of Ranolazine and eleven phase I metabolites in human plasma by
liquid chromatography-atmospheric pressure chemical ionization mass spectrometry
with selected-ion monitoring .,Journal of Chromatography A, 1995, 712(1), 50-60
24. Rodrigo,A.S, Thiago B, Pierina S.B,Enantioselective analysisof Ranolazine and Desmethyl ranolazine in microsomal medium
using dispersive liquid-liquid microextraction and LC-MS/MS.
, J.Bioanalysis, 5(2), 171-183
25. Tan Q, Zhu R, Li H, Fang P, Yan M, Zhang Q, Peng W,
Development and Validation of a,sensitive,U-HPLC-MS/MS, method,
with electrospray ionization
for quantitation of Ranolazine in human plasma:
Application to a clinical pharmacokinetic study. , Journal of Chromatography B,
2012, 901, 119-124
26. Wang Y, Chen X, Sun Z, Yang Y, Liu W, Zhong D,
Development and Validation of a sensitive LC-MS/MS assay for
simultaneous quantitataion of Ranolazine and its three
metabolites in human plasma., Journal of Chromatography
B analyt Technology Biomed Life Sciences, 2012, 10(6), 889-890
27. Bhaumik U, Ghosh A, Sarkar A,,BoseA, Selvan P, Sengupta P, Chakraborty U, Ghosh D,
Pal T, Determination of Ranolazine in human plasma by LC-MS/MS and
its application in bioequivalence study., Journal of Pharmaceutical and
Biomedical Analysis, 2008, 48(5), 1404-1410
28. Luo X, Zhai Z, Wu X, Shi Y, Chen L, Li Y, Analytical
and semi-preparative resolution
of Ranolazine enantiomers by,liquid,chromatography using
polysaccharide chiral stationary phases., Journal of separation
science, 2006, 29(1), 164-171
29. Laha T, Padhy D, Sen S, A Validated
stability indicating reversed phase high performance liquid chromatography
method of Ranolazine Dihydrochloride and characterization of its
degradation products., International journal of Pharmacy and Pharmaceutical
sciences, 2013, 5(1), 61-66
30. Tang JY, Wang w, Li L, Zhang CG, Wang DM, Sun L, Analysis of
primary metabolites of Ranolazine in dog urine by LC-MS(n).,
Yao Xue Xue Bao, 2012, 47(8), 1031-1038
31. Zhong J, Liu X.Q, Chen Y, Zhao X.P, Wang Y.S, Wang G.J,
Determination of Ranolazine in rat plasma by liquid
chromatography-electrospray ionization mass spectrometry.,
J. Chromatographia, 2006, 63(3-4), 123-127
32. Malati V, Reddy
A.R, Mukkanti K, Suryanarayana M.V, A novel reversed phase
stability indicating RP-UPLC method for the quantitative determination of
fifteen related substances in Ranolazine drug substance and drug
product., J. Talanta, 2012, 97, 563-373.
33. Ye YL, Yang XM, Determination of residual solvent
in Ranolazine by headspace gas chromatography. , Nan Fang
Yi Ke Da Xue Bao, 2008, 28(1), 134-135
34. J.K, K.R, R.K, N.S, Method development and Validation for the Estimation
of Ranolazine in Bulk and in Pharmaceutical Dosage Form by
UV-Spectrophotometry., Annals of Pharma Research.
35. Ugale J. B, Mulgund S. V, Development and Validation of
UV Spectrophotometric Area under cure method for Quantitative Estimation
of Ranolazine in API and Tablet Formulation., World journal of Pharmaceutical
Research, 2015,4(5), 2665-2672
36. Guada M, Imbuluzqueta E, Estella-Hermoso de
Mendoza A, Lana H, Dios-vieitez M.C, Blanco-Prieto M.J, Ultra high
performance liquid chromatography-tandem mass spectrometry method for
cyclosporine a quantification in biological samples and
lipid nanosystems.,
J Chromatogr B Analyt Technol Biome Life Sci., 2013,
927, 164-172
37. Killedar S, Pawar A, Nadaf S, Nale A, Tamboli U, Pishawikar S,
Novel analytical method development for some amide group containing drugs using
Bougainvillea spectabilis bract extracts., Asian Pac
J Trop Med, 2014
38. S. R, L. K.S, M. N, N. K, V. S, M. A, Colorimetric Determination
of Ranolazine in Bulk and Synthetic Mixture., An Indian
Journal of Analytical Chemistry, 8(4), 572-574
39. Sambasivarao V and P, R.S.ch, Development of Rapid
Visible Spectrophotometric Methods for the Estimation
of Ranolazine in Formulation., International Journal
of Researh in Pharmacy and Chemistry, 2011, 1(1), 66-72
40. Bidada J. P, Gonjari I. D, Raut C.
S, Bhutada C. J, Novel Spectrophotometric method for estimation
of Ranolazine in bulk and pharmaceutical dosage forms., Scholars
Research Library, 2011, 3(2), 1-4
41. Singh R, Singh P, Malik P, Singh T,
Nandrop, Spectrophotometric method Development and Validation for estimation
of Ranolazine in their bulk., Journal of Chromatography A,1995,
712(1), 55-60.
42. Gowda DV, Gowrav MP, Gangadharappa HV,
Khan MS, Preparation and Evaluation of mixture
of Eudragit and Ethylcellulose Microparticles loaded
with Ranolazine for Controlled Release., Journal of Young
Pharmacists, 2011, 3(3), 189-196
43. Nahid A, Pavani H, Development and Validation of
HPLC method for
simultaneous determination of Ranolazine and Dronederone in
bulk and pharmaceutical dosage forms., Indian Journal of research in Pharmacy
and Biotechnology, 2015, 2(6), 1524-1528
44. Avvaru R, Prabakaran V, Analytical method development and
validation of RP-HPLC method for simultaneous estimation
of ranolazine and Dronederone in bulk., International
Journal of Pharma Sciences, 2015, 5(3), 1030-1035