Journal : Acta Chromatographica
Article : Development and validation of a sensitive LC-MS/MS method for determination of valacyclovir in human plasma: Application to a bioequivalence study

Authors :
Patil, A. N.
Pravara Rural College of Pharmacy Department of Pharmacognosy Pravaranagar, Loni 413736 Maharashtra India,
Nirmal, S. A.
Pravara Rural College of Pharmacy Department of Pharmacognosy Pravaranagar, Loni 413736 Maharashtra India, nirmalsunil@rediffmail.com,
Chavan, A. K.
Pravara Rural College of Pharmacy Department of Pharmacognosy Pravaranagar, Loni 413736 Maharashtra India,
Zhou, L.
China Agricultural University Department of Applied Chemistry, College of Science Beijing 100193 China,
Xu, J.
China Agricultural University Department of Applied Chemistry, College of Science Beijing 100193 China,
Luan, L.
China Agricultural University Department of Applied Chemistry, College of Science Beijing 100193 China,
Ma, J.
China Agricultural University Department of Applied Chemistry, College of Science Beijing 100193 China,
Gong, Y.
Ministry of Agriculture Institute for the Control of Agrochemicals Beijing 100026 China,
Qin, D.
Ministry of Agriculture Institute for the Control of Agrochemicals Beijing 100026 China,
Pan, C.
China Agricultural University Department of Applied Chemistry, College of Science Beijing 100193 China,
Jinlong, M.
Zhejiang University Department of Chemical and Biological Engineering Hangzhou 310027 China,
Guobin, J.
Dalian Nationalities University Environment and Resources College Dalian 11660 China,
Bo, J.
Dalian Nationalities University Life Science College Dalian 116600 China,
Hua, J.
Zhejiang University Department of Chemical and Biological Engineering Hangzhou 310027 China,
Montejo, C.
Universidad CEU San Pablo Departamento de Ciencias Farmacéuticas y de la Alimentación, Área de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia 28668 Madrid Spain, montejo@ceu.es,
Civera, C.
Universidad Complutense de Madrid Departamento de Química Física II, Facultad de Farmacia 28040 Madrid Spain,
Barcia, E.
Universidad Complutense de Madrid Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia 28040 Madrid Spain,
Negro, S.
Universidad Complutense de Madrid Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia 28040 Madrid Spain,
Fernández-Carballido, A.
Universidad Complutense de Madrid Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia 28040 Madrid Spain,
Czauderna, M.
Polish Academy of Sciences The Kielanowski Institute of Animal Physiology and Nutrition 05-110 Jabłonna Poland, mr.czauderna@gmail.com,
Marounek, M.
Prague-Uhříněves The Institute of Animal Science Prague Czech Republic,
Duskova, D.
Prague-Uhříněves The Institute of Animal Science Prague Czech Republic,
Kowalczyk, J.
Polish Academy of Sciences The Kielanowski Institute of Animal Physiology and Nutrition 05-110 Jabłonna Poland,
Konda, R. K.
Hindu College of Pharmacy Department of Pharmaceutical Chemistry Amaravathi Road Guntur Andhrapradesh 522002 India, victory2ravi@yahoo.co.in,
Chandu, B. R.
Donbosco College of Pharmacy Department of Pharmaceutical Sciences Pulladigunta Guntur 522201 India,
Challa, B. R.
Nirmala College of Pharmacy Department of Pharmaceutical Analysis Madras Road Kadapa Andhrapradesh 516002 India, baluchalla_99@yahoo.com,
Chandrasekhar, K. B.
Jawaharlal Nehru Technological University Department of Chemistry Anantapur 515002 India,
Abstract : A simple, sensitive, and highly specific method has been developed for determination of valacyclovir (VL) in human plasma. The analytical procedure involves a solid-phase extraction method using Valacyclovir-D8 (VLD8) as an internal standard. Chromatographic separation was carried out on a reversed phase Zorbax, SB C18, 4.6 × 75 mm, 3.5μm column. Valacyclovir and Valacyclovir-D8 were detected with proton adducts at m/z 325.2 → 152.0 and 333.3 → 152.0 in multiple reaction monitoring (MRM) positive mode. The method was linear over the concentration range of 0.5–700.0 ng mL-1. The limit of detection (LOD) and limit of quantification (LOQ) for valacyclovir were 0.2 pg mL-1and 0.5 ng mL-1, respectively. The method was shown to be precise with the average within-run and between-run variations of 0.7 to 3.5% and 3.1 to 4.7%, respectively. The average within-run and between-run accuracies of the method throughout its linear range were 96.7 to 97.9 and 94.7 to 97.3%, respectively. The mean recoveries of valacyclovir and Valacyclovir-D8 from human plasma by the developed method were 99.17 ± 10.78% and 110.84 ± 8.74%, respectively. The method was successfully applied in bioequivalence study with 20 healthy male volunteers under fasting condition.

Keywords : valacyclovir, LC-MS/MS, solid-phase extraction, bioequivalence,
Publishing house : University of Silesia in Katowice
Publication date : 2013
Number : Vol. 25, no. 4
Page : 669 – 686

Bibliography
: 1 B.S. Anand, S. Katragadda, and Ashim K. Mitra, JPET, 311, 659 (2004)
2 M. Yadav, V. Upadhyay, P. Singhal, S. Goswami, and P.S. Shrivastav, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 877, 680 (2009)
3 M. Kasiari, E. Gikas, S. Georgakakou, M. Kazanis, and I. Panderi, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 864, 78 (2008)
4 J.M. Poirier, N. Radembino, and P. Jaillon, Drug Monit., 21, 129 (1999)
5 C. Dias, Y. Nashed, H. Atluri, and A. Mitra, Curr. Eye Res., 25, 243 (2002)
6 A.E. Thomsen, M.S. Christensen, M.A. Bagger, and B. Steffansen, Eur. J. Pharm. Sci., 23, 319 (2004)
7 A. Maes, B. Garre, N. Desmet, K. van der Meulen, H. Nauwynck, P. De Backer, and S. Croubels, Biomed. Chromatogr., 23, 132 (2009)
8 C. Pham-Huy, F. Stathoulopoulou, P. Sandouk, J.M. Scherrmann, S. Palombo, and C. Girre, J. Chromatogr. B Biomed. Sci. Appl., 732, 47 (1999)
9 A.S. Jadhav, D.B. Pathare, and M.S. Shingare, J. Pharm. Biomed. Anal., 43, 1568 (2007)
10 D.N. Fish, V.A. Vidaurri, and R.G. Deeter, Am. J. Health Syst. Pharm., 56, 1957 (1999)
11 K.M. Al Azzam, B. Saad, A. Makahleah, H.Y. Aboul-Enein, and A.A. Elbashir, Biomed. Chromatogr. (in press) (2009)
12 Guidance for Industry. Bioanalytical Method Validation, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM), May 2001
13 Guidance for Industry. Food-Effect Bioavailability and Fed Bioequivalence Studies. U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), December 2002
14 Guidance for Industry. Bioavailability and Bioequivalence Studies for Orally Administered Drug Products — General Considerations, U.S. Department of Health and Human Services. Food and Drug Administration, Center for Drug Evaluation and Research (CDER), March 2003
DOI :
Qute : Patil, A. N. ,Nirmal, S. A. ,Chavan, A. K. ,Zhou, L. ,Xu, J. ,Luan, L. ,Ma, J. ,Gong, Y. ,Qin, D. ,Pan, C. ,Jinlong, M. ,Guobin, J. ,Bo, J. ,Hua, J. ,Montejo, C. ,Civera, C. ,Barcia, E. ,Negro, S. ,Fernández-Carballido, A. ,Czauderna, M. ,Marounek, M. ,Duskova, D. ,Kowalczyk, J. ,Konda, R. K. ,Chandu, B. R. ,Challa, B. R. ,Chandrasekhar, K. B. ,Chandrasekhar, K. B. , Development and validation of a sensitive LC-MS/MS method for determination of valacyclovir in human plasma: Application to a bioequivalence study. Acta Chromatographica Vol. 25, no. 4/2013
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