Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Review Article Volume 5 Issue 5

A Systematic Review on the Analytical Techniques for the Quantification of Verapamil

Bangaru Divya and Mukthinuthalapati Mathrusri Annapurna*

GITAM Institute of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, India

*Corresponding Author: Mukthinuthalapati Mathrusri Annapurna, GITAM Institute of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, India.

Received: April 09, 2021; Published: April 30, 2021


  Verapamil is a calcium channel blocker. Verapamil is used for the treatment of high blood pressure and for the control of angina. In the present paper the authors have reviewed the analytical methods published in the literature for the estimation of Verapamil in pharmaceutical formulations and in biological samples.

Keywords: Verapamil; Calcium Channel Blocker; Analytical Techniques


  Verapamil is a calcium channel blocker with anti-anginal, anti-hypertensive and anti-arrhythmic activities Verapamil belongs to non-dihydro pyridine class of calcium channel blockers and it is administered as racemic mixture. The S-enantiomer of Verapamil is approximately 20 folds more potent than R-enantiomer [1,2]. Verapamil (Figure 1) has a molecular formula C27H38N2O4 and molecular weight 454.602 g/mole and is soluble in methanol, ethanol and water. The pKa value of Verapamil is 8.92.

Figure 1: Chemical structure of verapamil.

  Verapamil HCl is available as sustainable release caplets with brand names Calan SR (Labelled claim 180 mg.), extended release capsules (Labelled claim 300 mg.) and as injection (Labelled claim 5 mg, 10 mg: 2.5 mg/ml). Verapamil HCl is also available as tablets with label claim 40, 80 and 120 mg (Nicholas Piramal India Ltd). This article summarises the analytical techniques proposed by different authors for the quantification of Verapamil such as spectrophotometry [3-6] (Table 1), HPLC [8-12], UPLC [13], LC-MS/MS [14-16] and LC-MS [17] and table 2 represents some of the significant parameters observed in liquid chromatographic methods. The State Pharmacopoeia of Ukraine [18] has a monograph on the substance of verapamil hydrochloride and on verapamil hydrochloride tablets. To identify the substance of verapamil hydrochloride, State Pharmacopoeia of Ukraine offers UV-spectrophotometry, absorption spectrophotometry in the infrared region, TLC (mobile phase-diethylamine P-cyclohexane (15: 85), qualitative reaction to chlorides, quantitative determination-alkalimetry, potentiometric titration [18]. For identification of verapamil hydrochloride in tablets, the State Pharmacopoeia of Ukraine proposes UV-spectrophotometry, HPLC/ UV etc.







N-bromosuccinimide in perchloric acid




bromokresol green in an acetone medium




Bromothymol Blue and pH adjusted to 4 with NaOH and HCl




0.1N HCl and 0.1N NaOH (Differential spectroscopy)




Chloramine-T in HCl medium




Table 1: Review of spectrophotometric methods.

Mobile phase (v/v)






Acetonitrile: 0.025 M KH2PO4 buffer (pH 2.5)

Diltiazem (Internal standard)


Lichrospher 60



Human plasma


Metanol: Water: Tri ethyl amine (70: 30: 0.2)

Hypersil ODS





Mobile phase A: 50mM Ammonium phosphate (pH 4.5)

Mobile phase B: 50mM Ammonium phosphate: Acetonitrile (70:30)

Propranolol (Internal standard)

Capcell Pak C18



Rat plasma (Fluorescence detection)


Acetonitrile: Water (pH 2.7) (55: 45)




Verapamil and NSAIDs Human serum


Methanol: Water (pH 7.4) (70:30)




HPLC Synthesized metabolite (Impurity) Norverapamil


Ammonium formate: ortho phosphoric acid: Acetonitrile

Shimpak XR ODS


UPLC Related substances


Ammonium acetate: Methanol (20:80)

Ondansetron (Internal standard)

Purosphere C18

1 - 496

LC-ESI-MS/MS (Human plasma)



0.1% Ammonium formate: Acetonitrile (35:65)

Thermo Hypurity C 18


LC-MS/MS Human plasma



Mobile phase A: Acetonitrile: Water: Formic acid (5 : 95 : 0.1)

Mobile phase B: Acetonitrile: Formic acid (100 : 0.1)

Discovery C18


LC-MS/MS (Gradient mode)

(Caco-2 cell monolayers)


5 mM Ammonium acetate: Acetonitrile (Gradient mode)



LC-MS (Plasma and Intestinal fluid)



Table 2: Review of liquid chromatographic methods.


The present review helps the readers to do research in a new field apart from the presenting existing analytical techniques for the anti-anginal agent Verapamil.


  1. Basile J. “The role of existing and newer calcium channel blockers in the treatment of hypertension”. Journal of Clinical Hypertension (Greenwich)11 (2004): 621-629.
  2. Nafisur Rahman and Syed Najmul Hejaz Azmi. “Spectrophotometric method for the determination of Verapamil hydrochloride in pharmaceutical formulations using N-brmosuccinimide as oxidant”. Farmaco 7 (2004): 529-536.
  3. Marta Sulyma. “Spectrophotometric determination of Verapamil hydrochloride using Bromokresol Green”. Der Pharma Chemica5 (2018): 143-147.
  4. Salh DM. “Spectrophotometric determination of Isoptin (Verapamil hydrochloride) in Pharmaceutical Preparations”. Haitham Journal for Pure and Applied Science 3 (2017): 106-115.
  5. Leena Trivedi and Roshan Telrandhe “Differential spectrophotometric method for estimation and validation of Verapamil in Tablet dosage form”. International Journal of Pharmaceutics and Drug Analysis 11(2017): 419-422.
  6. Rahman N and Nasrul Hoda MD. “Spectrophotometric determination of Verapamil hydrochloride in drug formulations with chloramine-T as oxidant”. Analytical and Bioanalytical Chemistry 3 (2002): 484-489.
  7. Ivanova V., et al. “HPLC method for determination of Verapamil in human plasma after solid-phase extraction”. Journal of Biochemical and Biophysical Methods 6 (2008): 1297-1303.
  8. Milenović DM., et al. “Development and validation of an HPLC method for the determination of Verapamil residues in supports of cleaning procedure”. Journal of Analytical Chemistry 68 (2013): 545-551.
  9. Jhee OH., et al. “Direct determination of Verapamil in rat plasma by coupled column microbore-HPLC method”. Journal of Pharmaceutical and Biomedical Analysis 2 (2005): 405-410.
  10. Sultan N., et al. “Method development of Verapamil in presence of NSAIDs using RP-HPLC technique”. Bulletin- Korean Chemical Society7 (2011):2274 -2278.
  11. Pathade., et al. “Synthesis, characterization, and determination of metabolite of Verapamil hydrochloride by reversed-phase high performance liquid chromatography”. Chronicles of Young Scientists2 (2013): 164-169.
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  13. Dheeraj B., et al. “Determination of Verapamil in human plasma by tandem mass spectrometry”. Asian Journal of Chemistry9 (2009): 6785-6791.
  14. Chen Y., et al. “LC-MS/MS determination of Verapamil in human plasma and its application in bioequivalence evaluation”. Journal of Chinese Pharmaceutical Sciences7 (2012): 546-550.
  15. Logoyda L., et al. “HPLC MS/MS method development for the quantitative determination of verapamil hydrochloride from Caco-2 cell monolayers”. Pharmacia2 (2020): 63-69.
  16. Oliver von Richter., et al. “Rapid and highly sensitive method for the determination of Verapamil, [2H7] Verapamil and metabolites in biological fluids by liquid chromatography-mass spectrometry”. Journal of Chromatography B: Biomedical Sciences and Applications1 (2000): 137-147.
  17. The State Pharmacopeia of Ukraine. State Enterprise “Ukrainian Scientific Expert Pharmacopoeial Center of the Quality of Medicines” (2nd issue). Kharkiv: State Enterprise “Ukrainian scientific and experimental pharmacopoeial center for the quality of medicinal products 3 (2015): 1128.
  18. The European Pharmacopoeia (2016).


Citation: Bangaru Divya and Mukthinuthalapati Mathrusri Annapurna. “A Systematic Review on the Analytical Techniques for the Quantification of Verapamil". Acta Scientific Pharmaceutical Sciences 5.5 (2021): 56-59.


Copyright: © 2021 Bangaru Divya and Mukthinuthalapati Mathrusri Annapurna. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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