Gabapentin Bioequivalence Study: Quantification By Liquid Chromatography Coupled To Mass Spectrometry

The study was performed to compare the bioavailability of two gabapentin 400 mg capsule formulation (Gabapentin from Arrow Farmacêutica S/A as test formulation and Neurontin ® from Pfizer, Brazil, as reference formulation) in 26 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a one week wash out period. Plasma samples were obtained over a 48 hour interval. The gabapentin was analyzed by LC/MS/MS, in the presence of pracetamole as internal standard. With plasma concentration vs. time curves, data obtained from this metabolite, the following pharmacokinetics parameters were obtained: AUC 0-t, AUC 0-inf and C max. Geometric mean of gabapentin/Neurontin ® 400 mg individual percent ratio was 100.58% AUC 0-t, 101.35% for AUC 0-inf and 97.76% for C max. The 90% confidence intervals were 92.00 - 109.95%, 93.00 - 110.44%, 88.41 - 108.10%, respectively. Since the 90% confidence intervals for C max, AUC 0-t and AUC 0 -inf were within the 80 - 125% interval proposed by Food and Drug Administration, it was concluded that gabapentin 400 mg capsule was bioequivalent to Neurontin ® 400 mg capsule according to both the rate and extent of absorption. © 2011 Junior EA, et al.38187190Wattananat, T., Akarawut, W., Validated LC-MS-MS Method for the Determination of Gabapentin in Human Plasma: Application to a Bioequivalence Study (2009) J Chromatogr Sci, 47, pp. 868-871Stewart, B.H., Kagler, A.R., Thompson, P.R., Bockbrader, H.N., A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma (1993) Pharma Res, 10, pp. 276-281McLean, M.J., Gabapentin in the management of convulsive disorders (1999) Epilepsia, 40, pp. 39-50Goa, K.L., Sorkin, E.M., Gabapentin: A review of its pharmacological properties and clinical potential in epilepsy (1993) Drugs, 46, pp. 409-427Zhu, Z., Neirinck, L., High-performance liquid chromatographic method for the determination of gabapentin in human plasma (2002) J Chromatogr B Analyt Technol Biomed Life Sci, 779, pp. 307-312Sagirli, O., Cetin, S.M., Determination of gabapentin in human plasma and urine by high-performance liquid chromatography with UV-vis detection (2006) J Pharm Biomed Anal, 42, pp. 618-624Jalalizadeh, H., Souri, E., Tehrani, M.B., Jahangiri, A., Validated HPLC method for the determination of gabapentin in human plasma using precolumn derivatization with 1-fluoro-2,4-dinitrobenzene and its application to a pharmacokinetic study (2007) J Chromatogr B Analyt Technol Biomed Life Sci, 854, pp. 43-47Forrest, G., Sills, G.J., Leach, J.P., Brodie, M.J., Determination of gabapentin in plasma by high-performance liquid chromatography (1996) J Chromatogr B Analyt Technol Biomed Life Sci, 681, pp. 421-425Tang, P.H., Miles, M.V., Glauser, T.A., Degrauw, T., Automated microanalysis of gabapentin in human serum by high-performance liquid chromatography with fluorometric detection (1999) J Chromatogr B Analyt Technol Biomed Life Sci, 727, pp. 125-129Hassan, E.M., Belal, F., Al-Deeb, O.A., Khalil, N.Y., Spectrofluorimetric determination of vigabatrin and gabapentin in dosage forms and spiked plasma samples through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (2001) J. AOAC Int., 84, pp. 1017-1024Gauthier, D., Gupta, R., Determination of gabapentin in plasma by liquid chromatography with fluorescence detection after solid-phase extraction with a C18 column (2002) Clin Chem, 48, pp. 2259-2261Chung, T.C., Tai, C.T., Wu, H.L., Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gabapentin in human plasma (2006) J Chromatogr A, 119, pp. 294-298Bahrami, G., Kiani, A., Sensitive high-performance liquid chromatographic quantitation of gabapentin in human serum using liquid-liquid extraction and pre-column derivatization with 9-fluorenylmethyl chloroformate (2006) J Chromatogr B Analyt Technol Biomed Life Sci, 835, pp. 123-126Krivanek, P., Koppatz, K., Turnheim, K., Simultaneous isocratic HPLC determination of vigabatrin and gabapentin in human plasma by dansyl derivatization (2003) Ther Drug Monit, 25, pp. 374-377Chang, S.Y., Wang, F.Y., Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gabapentin in human plasma (2004) J Chromatogr B Analyt Technol Biomed Life Sci, 799, pp. 265-270Wolf, C.E., Saady, J.J., Poklis, A., Determination of gabapentin in serum using solid phase extraction and gas-liquid chromatography (1996) J Anal Toxicol, 20, pp. 498-501Kushnir, M.M., Cossett, J., Brown, P.I., Urry, F.M., Analysis of gabapentin in serum and plasma by solid-phase extraction and gas chromatography-mass spectrometry for therapeutic drug monitoring (1999) J Anal Toxicol, 23, pp. 1-6Borrey, D.C., Godderis, K.O., Engelrelst, V.I., Bernard, D.R., Langlois, M.R., Quantitative determination of vigabatrin and gabapentin in human serum by gas chromatography-mass spectrometry (2005) Clin Chim Acta, 354, pp. 147-151Gambelunghe, C., Mariucci, G., Tantucci, M., Ambrosini, M.V., Gas chromatography-tandemmass spectrometry analysis of gabapentin in serum (2005) Biomed Chromatogr, 19, pp. 63-67Matar, K.M., Abdel-Hamid, M.E., Rapid tandem mass spectrometric method for determination of gabapentin in human plasma (2005) Chromatographia, 61, pp. 499-504Ramakrishna, N.V.S., Vishwottam, K.N., Koteshwara, M., Maroj, S., Santosh, M., Rapid quantification of gabapentin in human plasma by liquid chromatography/tandemmass spectrometry (2006) J Pharm Biomed Anal, 40, pp. 360-368Ifa, D.R., Falci, M., Moraes, M.E., Bezerra, F.A., Moraes, M.O., Gabapentin quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study (2001) J Mass Spectrom, 36, pp. 188-194Ji, H.Y., Jeong, D.W., Kim, Y.H., Kim, H.H., Yoon, Y.S., Determination of gabapentin in human plasma using hydrophilic interaction liquid chromatography with tandem mass spectrometry (2006) Rapid Commun Mass Spectrom, 20, pp. 2127-2132Carlsson, K.C., Reubsaet, J.L., Sample preparation and determination of gabapentin in venous and capillary blood using liquid chromatography-tandem mass spectrometry (2004) J Pharm Biomed Anal, 34, pp. 415-423Park, J.H., Jhee, O.H., Park, S.H., Lee, J.S., Lee, M.H., Validated LC-MS/ MS method for quantification of gabapentin in human plasma: Application to pharmacokinetic and bioequivalence studies in Korean volunteers (2007) Biomed Chromatogr, 21, pp. 829-83

Determination Of Herbicides And A Metabolite In Human Urine By Liquid Chromatography-electrospray Ionization Mass Spectrometry

A method was developed to determine simazine, atrazine and their metabolite, 2-chloro-4,6-diamino-1,3,5-triazine, in urine. The presence of these herbicides in urine may reflect possible exposure to pesticides. Sample preparation involved protein precipitation and solid-phase extraction. The samples were analyzed by high-performance liquid chromatography-mass spectrometry. The detection limits were 0.4 μg/l and the analytes have a linear response in the interval 6-800 μg/l. The precision of the method was reflected in the RSD of <2.4% for the herbicides studied. Based on the detectable herbicide levels from spiked urine samples collected from unexposed volunteers, this method can be used to determine the low levels necessary for establishing reference values of the selected herbicides and the metabolite. © 2002 Elsevier Science B.V. All rights reserved.98701/02/15375380Barceló, D., (1991) Analyst, 116, p. 681Günther, W.J., Kettrup, A., (1989) Chromatographia, 28, p. 209Abián, J., Durand, G., Barceló, D., (1993) J. Agric. Food Chem., 41, p. 1264Durand, G., Forteza, R., Barceló, D., (1989) Chromatographia, 28, p. 597Pereira, W.E., Rostad, C.E., Leiker, T.J., (1990) Anal. Chim. Acta, 228, p. 69Maroni, M., Colosio, C., Fait, A., (2000) Toxicology, 143, p. 97Hanioka, N., Jinno, H., Tanaka-Kagawa, T., Nishimura, T., Ando, M., (1999) Toxicol. Appl. Pharmacol., 156, p. 195Verheij, E.R., Van der Greef, J., La Vos, G.F., Van der Pol, W., Niessen, W.M.A., (1989) J. Anal. Toxicol., 13, p. 8Hogendoorn, E., Van Zoonen, P., (2000) J. Chromatogr. A, 892, p. 435Mauer, H.H., (1998) J. Chromatogr. B, 713, p. 3Polettini, A., (1999) J. Chromatogr. B, 733, p. 47Sacchero, G., Apone, S., Sarzanini, C., Mentasti, E., (1994) J. Chromatogr. A, 668, p. 365Kumazawa, T., Sato, K., Seno, H., Suzuki, O., (1992) Forensic Sci. Int., 54, p. 159Chasin, A.A.M., Chasin, M., Salvador, M.C., (1994) Rev. Farm. Bioquim., 30, p. 49Jenke, D.R., (1998) Instr. Sci. Technol., 26, p.

Manejo de irrigação e fertilização nitrogenada para o feijoeiro na região dos cerrados Irrigation timing and nitrogen fertilization for common bean crop in the cerrado region

Este trabalho foi desenvolvido na área experimental da Embrapa-Centro de Pesquisa Agropecuária dos Cerrados (CPAC) com o objetivo de estudar os efeitos de diferentes regimes hídricos e de diferentes doses de N sobre a produtividade e componentes de produção de feijão Pérola (Phaseolus vulgaris L.) cultivado após o milho, na região de cerrado. As aplicações de água foram feitas quando a tensão de água no solo, medida a 10 cm de profundidade, atingia valores de 41, 55, 75 e 300 kPa. As doses de N testadas foram: 0, 40, 80 e 160 kg/ha. As doses foram parceladas em duas aplicações, a saber: a metade, aplicada por ocasião da emergência das plântulas, e o restante, no início do estádio de florescimento da cultura. A máxima produtividade foi obtida com as irrigações quando a tensão de água no solo era de 41 kPa, medida a 10 cm de profundidade. As doses de N que propiciaram as máximas produtividades variaram com a tensão de água no solo utilizada para o controle da irrigação. A quantidade de água aplicada para uma produtividade superior a 4.800 kg/ha foi em torno de 450 mm. O valor da relação entre a produtividade e a lâmina de água aplicada aumentou com o aumento da tensão de água no solo e das doses de N.<br>This study was carried out in the experimental field of the Embrapa-Centro de Pesquisa Agropecuária dos Cerrados (CPAC) to determine the irrigation timing and the nitrogen amounts for common bean crop (Phaseolus vulgaris L.), cultivated after corn, in the cerrado region. Water was applied when soil-water tension, measured at a depth of 10 cm reached values of 41, 55, 75 and 300 kPa. The nitrogen doses were splited in two applications. Half doses was applied just after germination and the other half at the initial flowering stage. The highest yield was obtained with irrigation at 41 kPa, measured at a depth of 10 cm. In relation to nitrogen doses, maximum yield was attained with variable soil water tension value used to control water application. The total amount of water applied to common bean crop for a yield over 4,800 kg/ha was approximately 450 mm. The value of the relationship between yield and applied water increased as soil water tension and nitrogen doses increased