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Enantiomeric Separation and Validation of D-Isomer in Pemetrexed Disodium–An Anti-Cancer Agent using Chiral HPLC


Affiliations
1 GITAM Institute of Science, GITAM(Deemed to be University), Vishakapatnam, India
2 Department of Pharmaceutical Ananlysis & Quality Assurance, GITAM Institute of Pharmacy, GITAM(Deemed to be University), Vishakapatnam, India
     

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Pemetrexed disodium is an anti-cancer agent. It is an anti-folate drug used for the treatment of malignant pleural mesothelioma and non-small cell lung cancer. In the present study the authors have proposed a chiral HPLC method for the separation and determination of Pemetrexed disodium and its D-isomer using Chiralpak AD-H (250 x 4.6 mm, 5 μm) column within a run time of 30 mins. A mixture of n-Hexane: Ethanol: Isopropyl alcohol: TFA (250:650:100:1) was the final optimized mobile phase composition after many trials for the separation of D-isomer of Pemetrexed disodium (at 35°C) using Waters Alliance 2695 series HPLC system with 2998 photodiode array detector (UV detection at 240 nm). The method is very much useful for the pharmacokinetic studies as well as the metabolite study in vitro and in vivo for the determination of therapeutic activities of optical isomers.

Keywords

Pemetrexed Disodium, HPLC, D-Isomer, Validation.
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  • Jones RJ, Twelves CJ. Pemetrexed: a multi targeted antifolate (ALIMTA, LY-231514). Expert Review of Anticancer Therapy. 2; 2002:13-22.

  • Shih C, Chen VJ, Gossett LS, Gates SB, MacKellar WC, Habeck LL, et al. LY231514, a pyrrolo [2,3-d] pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Research. 57(6); 1997:1116-1123.

  • Paz-Ares L, Bezares S, Tabernero JM, Castellanos D, CortesFunes H. Review of a promising new agent – pemetrexed disodium. Cancer 97(8) Suppl; 2003: 2056-2063.

  • Hanauske AR, Chen V, Paoletti P, Niyikiza C. Pemetrexed disodium: A novel antifolate clinically active against multiple solid tumors. Oncologist. 6(4); 2001: 363-373.

  • Bischof M,Weber KJ, Blatter J, Wannenmacher M, Latz D. Interaction of Pemetrexed disodium (ALIMTA, multi targeted antifolate) and irradiation in vitro. International Journal of Radiation Oncology, Biology, Physics 52(5); 2002: 1381-1388.

  • Roland J. W. Meesters, Robin Cornelissen, Rob J. van Klaveren, Robert de Jonge, Ethan den Boer, Jan Lindemans, Theo M. Luider. A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multitargeted anti-folate Pemetrexed in plasma from lung cancer patients. Analytical and Bioanalytical Chemistry, 2010, 398, (78), 2943-2948.

  • Marcel P.Stoop, SabineVisser , Evertvan Dijk , Joachim G.J.V.Aerts , Bruno H.Stricker ,Theo M.Luider. A new quantification method for assessing plasma concentrations of Pemetrexed and its polyglutamate metabolites. Journal of Pharmaceutical and Biomedical Analysis. 128 (5); 2016: 1-8.

  • Laurent PR, Stephen JC, Michael B, James FB. Highly sensitive analysis of the antifolate pemetrexed sodium, a new cancer agent, in human plasma and urine by high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications. 765(2); 2001: 135-140.

  • Vamsi Krishna Galla, V. Archana, Rajeswari Jinka. A new rapid stability indicating RP-PDA-UPLC method for the estimation of assay of Pemetrexed disodium-An anti-lung cancer drug from lyophilized parenteral formulation. Journal of Applied Pharmaceutical Science. 7 (10); 2017: 131-137.

  • Ramulu K, Rao BM, Madhavan P, Lalitha Devi M, Srinivasu MK and Chandrasekhar KB. A validated chiral LC method for the determination of enantiomeric purity of Pemetrexed disodium on an amylose-based chiral stationary phase. Chromatographia. 65(3-4); 2007: 249-252.

  • Saravanan G, Suryanarayana MV, Jadhav MJ, Ravikumar M, Someswararao N and Acharyulu PVR. A stability-indicating LC assay method for Pemetrexed disodium., 2007, 66, 431-434.

  • Thahera Banu, Murali Balaram Varanasi, Mushraff Ali Khan M, Sharma JVC, Bhanu Teja B, Swaroop Kumar V and Habibuddin M. Validated reverse phase HPLC method for the determination of Pemetrexed disodium in pharmaceutical dosage forms. Oriental Journal of Chemistry. 26(4); 2010: 1325-1332.

  • Rakesh Gupta K, Balakumar C, Anjaneyulu V, Karpakavalli M, Lakshmi Narayanan B, Ranjith Kumar D, Kumar EP. Development and validation of RP-HPLC method for related substance of Pemetrexed disodium. International Journal of Pharmaceutical Sciences Review and Research. 15(2); 2012: 133-137.

  • Ankit DP, Shalin KP, Sen DJ and Patel CN. Development and validation of high performance liquid chromatographic and UV spectrophotometric method for estimation of Pemetrexed disodium in bulk drug and pharmaceutical formulation. International Journal of Drug Development and Research. 3(2); 2011: 301-307.

  • Janaki Pathi P, Saifulla Khan P, Raveendra Reddy P and Appala Raju N. Visible spectrophotometric estimation of Pemetrexed disodium in pharmaceutical formulations. Journal of Pharmacy Research 4(2); 2011: 524-525.

  • Umesh SD, Nagaraj PS, Suresh MT. Electrochemical oxidation and determination of an anticancer drug pemetrexed disodium. Asian Journal of Pharmaceutical and Clinical Research 10(3); 2017: 492-496.

  • ICH Q2 (R1) Validation of analytical procedures: Text and methodology (2005).


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  • Enantiomeric Separation and Validation of D-Isomer in Pemetrexed Disodium–An Anti-Cancer Agent using Chiral HPLC

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Authors

S. Hemchand
GITAM Institute of Science, GITAM(Deemed to be University), Vishakapatnam, India
R. Ravi Chandra Babu
GITAM Institute of Science, GITAM(Deemed to be University), Vishakapatnam, India
Mukthinuthalapati Mathrusri Annapurna
Department of Pharmaceutical Ananlysis & Quality Assurance, GITAM Institute of Pharmacy, GITAM(Deemed to be University), Vishakapatnam, India

Abstract


Pemetrexed disodium is an anti-cancer agent. It is an anti-folate drug used for the treatment of malignant pleural mesothelioma and non-small cell lung cancer. In the present study the authors have proposed a chiral HPLC method for the separation and determination of Pemetrexed disodium and its D-isomer using Chiralpak AD-H (250 x 4.6 mm, 5 μm) column within a run time of 30 mins. A mixture of n-Hexane: Ethanol: Isopropyl alcohol: TFA (250:650:100:1) was the final optimized mobile phase composition after many trials for the separation of D-isomer of Pemetrexed disodium (at 35°C) using Waters Alliance 2695 series HPLC system with 2998 photodiode array detector (UV detection at 240 nm). The method is very much useful for the pharmacokinetic studies as well as the metabolite study in vitro and in vivo for the determination of therapeutic activities of optical isomers.

Keywords


Pemetrexed Disodium, HPLC, D-Isomer, Validation.

References