SIMULTANEOUS DETERMINATION OF 2-CHLORO METHYL PROPIONATE, 1,4-DI-BROMO BUTANE AND PARA ANISIC ALDEHYDE IN MEBEVERINE HYDROCHLORIDE API BY GAS CHROMATOGRAPHY-MASS SPECTROMETRIC WITH SELECTED-ION-MONITORING MODE
Objective: To develop an accurate, precise and linear gas chromatography-mass spectrometric (GC-MS) selected-ion-monitoring (SIM) method for
quantitative estimation of 2-chloro methyl propionate (2-CMP), 1,4-dibromo butane and para anisic aldehyde (PAA) as an genotoxic impurities in
mebeverine HCl API (MEB) at ppm level and validated as per International Council of Harmonization (ICH) guidelines.
Methods: This method used in SIM mode mass selective detection was developed and validated for the trace level analysis of three impurities. All
these three impurities are simultaneously determined by a GC-MS method using VF-624 Capillary column (60 mÃ—0.32 mmÃ—1.80 Âµm) with Helium as
carrier gas and a flow rate of 2.0 mL/minutes. Chromatographic separation of 2-CMP, 1,4-DBB, and PAA was achieved in 7.91, 13.69, 18.45 minutes
and m/z values were 63, 55, 135 on SIM mode.
Results: The method was linear for 2-CMP, 1,4-DBB and PAA in mebeverine HCl 1.90 Âµg/ml to 7.5 Âµg/ml, respectively. The coefficient of correlation
) for the 2-CMP, 1,4-DBB and PAA was better than 0.999. The limit of detection obtained was 0.28, 0.35, 0.22 Âµg/ml and the limit of quantification
(LOQ) obtained was 0.85, 1.06, 0.66 Âµg/ml. The method was fully validated, complying Food and Drug Administration, ICH and European Medicines
Agency guidelines. Furthermore, verified precision, accuracy, LOQ precision, LOQ accuracy, ruggedness, and robustness.
Conclusion: The proposed method is specific, accurate, precise, linear, rugged and robust for the determination of the three genotoxic impurities in
API of mebeverine HCl, and hence, is of wide applicability in pharmaceutical industries.
Keywords: 2-chloro methyl propionate, 1,4-dibromo butane, Para anisic aldehyde, Mebeverine HCl, Gas chromatography-mass spectrometric, Method
development, Method validation.
Ramadevi, Srikanth S, Kumar AA. RP-HPLC method development
and validation for simultaneous quantitative estimation of mebeverine
Asian J Pharm Clin Res, Vol 9, Suppl. 2, 2016, 168-175
Babu et al.
HCl and chlordiazepoxide in capsules. Int J Pharm Pharm Sci
Reddy PR, Reddy VK, Goud ES, Reddy YR. Development and
validation of a ultra performance liquid chromatographic method for
assay of mebeverine HCl. Int J Pharm Pharm Sci 2014;6 Suppl 2:442-5.
Kakasaheb NA, Ramakrishna K, Srinivasarao V. Method determination
and validation of genotoxic impurities methyl methane soulfonate and
methyl iodide in montelukast sodium drug substance by GC-MS. World
J Pharm Res 2014;3(8):557-67.
Maddala VL, Ray PC, Venugopal K, Rao KM. A sensitive and selective
GC-MS analysis of process related genotoxic impurities of nebivolol
hydrochloride. Asian J Chem 2016;28(4):811-3.
Sarat M, Ramakrishna M, Suresh Y, Harikrishna S, Rambabu C,
Kishore K, et al. Low-level determination of residual methyl methane
sulfonate and ethyl methane sulfonate in pharmaceuticals by gas
chromatography with mass spectrometry. E J Chem 2010;7(2):629-35.
Veenaeesh P, Manikumar G, Manjusha P, Padmasri A. Determination
of methyl methane sulfonate, ethyl methane sulfonate and isopropyl
methane sulfonate impurities in lopinavir API by GC/MS/MS using
electron ionization. Int J Pharm Res Rev 2014;3(2):11-6.
ICH. Guidelines Q2B Validation of Analytical Procedures Methodology
in Proceedings of International Conference on Harmonization.
Rockville, USA; 1996. p. 1-10.
Belal TS, Mahrous MS, Abdel-Khalek MM, Daabees HG, Khamis MM.
Validated HPTLC method for the simultaneous determination
of alfuzosin, terazosin, prazosin, doxazosin and finasteride in
pharmaceutical formulations. Anal Chem Res 2014;1:23-31.
Sriboonvorakul N, Leepipatpiboon N, Dondorp AM, Pouplin T,
White NJ, Tarning J, et al. Liquid chromatographic-mass spectrometric
method for simultaneous determination of small organic acids
potentially contributing to acidosis in severe malaria. J Chromatogr B
Analyt Technol Biomed Life Sci 2013;941:116-22.
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