Abstract
Six nonsteroidal anti-inflammatory drugs (NSAIDs) in human plasma samples were analyzed by liquid chromatography (LC)-electrospray ionizationtandem mass spectrometry (MS-MS) using a hydrophilic polymer column (MSpak GF-310 4B), which enabled direct injection of crude biological samples. Separation of the six NSAIDs, alminoprofen, flurbiprofen, ibuprofen, pranoprofen, tiaprofenic acid, and zaltoprofen, was carried out using gradient elution with 10 mM ammonium acetate/acetonitrile. The mass spectra obtained by LC-single stage MS showed base peak ions due to [M+H]+ for alminoprofen, zaltoprofen, tiaprofenic acid, and pranoprofen, and [M-H]- for ibuprofen and flurbiprofen. Product ions were produced from each [M+H]+ or [M-H]- ion in the tandem mode. Quantitation was performed by multiple reaction monitoring with switching from positive to negative ion mode and vice versa. All drugs spiked into plasma showed recoveries of 77.0%–88.2%. The regression equations for the six drugs showed excellent linearity in the range of 0.01–25 μg/ml of plasma, and limits of detection were in the range of 0.002–0.005 μg/ml. Limits of quantitation were 0.01–0.02 μg/ml. Intraday and interday coeffi cients of variation for all drugs in plasma were not greater than 8.1%. The accuracy of quantitating the six drugs was in the range of 94.5%–110%. Data obtained from actual determinations of the levels of alminoprofen, pranoprofen, and ibuprofen in human plasma after oral administration are also presented.
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References
Burke A, Smyth E, Fitzgerald GA (2006) Analgesic-antipyretic agents; pharmacotherapy of gout. In: Brunton LL, Lazo JS, Parker KL (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York, pp 671–715
Magill P, Ridgway PF, Conlon KC, Neary P (2006) A case of probable ibuprofen-induced acute pancreatitis. J Pancreas 7:311–314
Wood DM, Monaghan J, Streete P, Jones AL, Dargan PI (2006) Fatality after deliberate ingestion of sustained-release ibuprofen: a case report. Crit Care 10:R44
Scelzi S, Giubilei G, Bartoletti R, Loro FD, Mondaini N, Crisci A (2004) Nephrogenic adenoma of bladder after ibuprofen abuse. Urology 64:1030–1031
Makino K, Itoh Y, Teshima D, Oishi R (2004) Determination of nonsteroidal anti-inflammatory drugs in human specimens by capillary zone electrophoresis and micellar electrokinetic chromatography. Electrophoresis 25:1488–1495
Petrović M, Debeljak Ž, Blažević N (2005) Optimization of gas chromatographic method for the enantioseparation of arylpropionic non-steroidal anti-inflammatory drug methyl esters. J Pharm Biomed Anal 39:531–534
Caviglioli G, Valeria P, Brunella P, Sergio C, Attilia A, Gaetano B (2002) Identification of degradation products of ibuprofen arising from oxidative and thermal treatments. J Pharm Biomed Anal 30:499–509
Verenitch SS, Lowe CJ, Mazumder A (2006) Determination of acidic drugs and caffeine in municipal wastewaters and receiving waters by gas chromatography-ion trap tandem mass spectrometry. J Chromatogr A 1116:193–203
Canaparo R, Muntoni E, Zara GP, Pepa CD, Berno E, Costa M, Eandi M (2000) Determination of ibuprofen in human plasma by high-performance liquid chromatography: validation and application in pharmacokinetic study. Biomed Chromatogr 14:219–226
Farrar F, Letzig L, Gill M (2002) Validation of a liquid chromatographic method for the determination of ibuprofen in human plasma. J Chromatogr B 780:341–348
Sharma PK, Garg SK, Narang A (2003) Pharmacokinetics of oral ibuprofen in premature infants. J Clin Pharmacol 43: 968–973
Teng XW, Wang SWJ, Davies NM (2003) Stereospecific highperformance liquid chromatographic analysis of flurbiprofen: application to pharmacokinetic studies. J Pharm Biomed Anal 33:95–100
Pehourcq F, Matoga M, Jarry C, Bannwarth B (2004) HPLC microdetermination of flurbiprofen enantiomers in plasma with a glycopeptide-type chiral stationary phase column. Biomed Chromatogr 18:330–334
Swart H, Breytenbach JC, Hadgraft J, Du Plessis J (2005) Synthesis and transdermal penetration of NSAID glycoside esters. Int J Pharm 301:71–79
Fan Y, Feng YQ, Da SL, Wang ZH (2005) In-tube solid phase microextraction using a β-cyclodextrin coated capillary coupled to high performance liquid chromatography for determination of non-steroidal anti-inflammatory drugs in urine samples. Talanta 65:111–117
De Oliveira ARM, Cesarino EJ, Bonato PS (2005) Solid-phase microextraction and chiral HPLC analysis of ibuprofen in urine. J Chromatogr B 818:285–291
Marchese S, Gentili A, Perret D, D’Ascenzo G, Pastori F (2003) Quadrupole time-of-flight versus triple-quadrupole mass spectrometry for the determination of non-steroidal anti-inflammatory drugs in surface water by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 17:879–886
Hilton MJ, Thomas KV (2003) Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatographyelectrospray tandem mass spectrometry. J Chromatogr A 1015:129–141
Bonato PS, Lama MPD, De Carvalho R (2003) Enantioselective determination of ibuprofen in plasma by high-performance liquid chromatography-electrospray mass spectrometry. J Chromatogr B 796:413–420
Quintana JB, Reemtsma T (2004) Sensitive determination of acidic drugs and triclosan in surface and wastewater by ionpair reverse-phase liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 18:765–774
Ferrer I, Thurman EM (2005) Measuring the mass of an electron by LC/TOF-MS: a study of “gtwin ions”. Anal Chem 77:3394–3400
Lee HW, Seo JH, Kim YW, Jeong SY, Lee KT (2006) Determination of zaltoprofen in human plasma by liquid chromatography with electrospray tandem mass spectrometry: application to a pharmacokinetic study. Rapid Commun Mass Spectrom 20:2675–2680
Arinobu T, Hattori H, Iwai M, Ishii A, Kumazawa T, Suzuki O, Seno H (2002) Liquid chromatographic.mass spectrometric determination of haloperidol and its metabolites in human plasma and urine. J Chromatogr B 776:107–113
Lee X-P, Kumazawa T, Sato J, Shoji Y, Hasegawa C, Karibe C, Arinobu T, Seno H, Sato K (2003) Simple method for the determination of benzodiazepines in human body fluids by high-performance liquid chromatography-mass spectrometry. Anal Chim Acta 492:223–231
Lee X-P, Kumazawa T, Fujishiro M, Hasegawa C, Marumo A, Shoji Y, Arinobu T, Seno H, Sato K (2006) Simple method for determination of triazolam in human plasma by highperformance liquid chromatography/tandem mass spectrometry. J Pharm Biomed Anal 41:64–69
Fujimaki K, Lee X-P, Kumazawa T, Sato J, Sato K (2006) Determination of some antiallergic drugs in human plasma by direct-injection high-performance liquid chromatographytandem mass spectrometry. Forensic Toxicol 24:8–16
Umezawa H, Lee X-P, Arima Y, Hasegawa C, Izawa H, Kumazawa T, Sato K (2008) Simultaneous determination of β-blockers in human plasma using liquid chromatographytandem mass spectrometry. Biomed Chromatogr 22:702–711
Umezawa H, Lee X-P, Arima Y, Hasegawa C, Marumo A, Kumazawa T, Sato K (2008) Determination of diazepam and its metabolites in human urine by liquid chromatography/tandem mass spectrometry using a hydrophilic polymer column. Rapid Commun Mass Spectrom 22:2333–2341
Hattori H, Hirata Y, Hamajima M, Kaneko R, Ito K, Ishii A, Suzuki O, Seno H (2009) Simultaneous analysis of aconitine, mesaconitine, hypaconitine, and jesaconitine in whole blood by LC-MS-MS using a new polymer column. Forensic Toxicol 27:7–11
Tod M, Pobel C, Le Gros V, Louchahi K, Petitjean O, Brion N, Garcia-Mace JL (1995) A population pharmacokinetic study of alminoprofen penetration into synovial fluid. Biopharm Drug Dispos 16:627–634
Daymond TJ, Herbert R (1983) Pharmacokinetic studies of a high dose of tiaprofenic acid in patients suffering from arthritis. Br J Clin Pharmacol 15:157–158
Fujimura A, Kajiyama H, Kumagai Y, Nakashima H, Sugimoto K, Ebihara A (1989) Chronopharmacokinetic studies of pranoprofen and procainamide. J Clin Pharmacol 29: 786–790
Winek CL, Wahba WW, Winek CL Jr., Balzer TW (2001) Drug and chemical blood-level data 2001. Forensic Sci Int 122:107–123
Cardoe N, De Silva M, Glass RC, Risdall PC (1977) Serum concentrations of flurbiprofen in rheumatoid patients receiving flurbiprofen over long periods of time. Curr Med Res Opin 5:21–25
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Lee, XP., Kumazawa, T., Hasegawa, C. et al. Determination of nonsteroidal anti-inflammatory drugs in human plasma by LC-MS-MS with a hydrophilic polymer column. Forensic Toxicol 28, 96–104 (2010). https://doi.org/10.1007/s11419-010-0096-8
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DOI: https://doi.org/10.1007/s11419-010-0096-8