Development and Validation of a Simple and Reliable LC-MS/MS Method for the Determination of Acetazolamide, an Effective Carbonic Anhydrase Inhibitor, in Plasma and its Application to a Pharmacokinetic Study

Abstract

A simple, rapid and accurate liquid chromatography – tandem mass spectrometry method was developed and validated for the quantification of acetazolamide in beagle plasma using sulfadiazine as the internal standard. After extraction by acetonitrile, the analytes were separated by a rapid gradient elution with acetonitrile and water as the mobile phase on a SHIMADZU VP-ODS C18 column and then detected by an API 4000 triple-quadrupole mass spectrometer using electrospray ionization in negative ion mode. Multiple reaction monitoring was performed on the ion transitions of m/z 220.9→83.3 (acetazolamide) and m/z 248.9→185.0 (sulfadiazine). The plasma concentration of acetazolamide in beagle dogs showed good linearity over the range of 0.20~50 μg/mL, and the intra- and inter-day variations were small with high accuracy and absolute recovery. Both analytes can maintain stable during the whole experimental process. The developed method was successfully applied to the pharmacokinetic study of acetazolamide extended-release capsules after oral administration to beagle dogs.

Key words

acetazolamide - LC-MS/MS - pharmacokinetics - beagle dogs

• References

• 1 Kaur IP, Smitha R, Aggarwal D et al. Acetazolamide: future perspective in topical glaucoma therapeutics. Int J Pharm 2002; 248: 1-14
• 2 Dumont L, Mardirosoff C, Tramèr MR. Efficacy and harm of pharmacological prevention of acute mountain sickness: quantitative systematic review. BMJ (Clinical research ed.) 2000; 321: 267-272
• 3 Chow T, Browne V, Heileson HL et al. Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial. Arch Intern Med 2005; 165: 296-301
• 4 Rivera-Ch M, Huicho L, Bouchet P et al. Effect of acetazolamide on ventilatory response in subjects with chronic mountain sickness. Respir Physiol Neurobiol 2008; 162: 184-189
• 5 Sheng W, Dong M, Zhou J et al. Down regulation of CAII is associated with tumor differentiation and poor prognosis in patients with pancreatic cancer. J Surg Oncol 2013; 107: 536-543
• 6 Katayama F, Miura H, Takanashi S et al. Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies. Brain Dev 2002; 24: 150-154
• 7 Okazawa H, Yamauchi H, Sugimoto K et al. Differences in vasodilatory capacity and changes in cerebral blood flow induced by acetazolamide in patients with cerebrovascular disease. J Nucl Med 2003; 44: 1371-1378
• 8 Zarghi A, Shafaati A. Rapid determination of acetazolamide in human plasma. J Pharm Biomed Anal 2002; 28: 169-172
• 9 Ichikawa N, Naora K, Hirano H et al. Quantitation of acetazolamide in rat plasma, brain tissue and cerebrospinal fluid by high-performance liquid chromatography. J Pharm Biomed Anal 1998; 17: 1415-1421
• 10 Chapron DJ, White LB. Determination of acetazolamide in biological fluids by reverse-phase high-performance liquid chromatography. J Pharm Sci 1984; 73: 985-989
• 11 Herráez-Hernández R, Campíns-Falcó P, Sevillano-Cabeza A. Determination of acetazolamide in human urine samples by reversed-phase high-performance liquid chromatography in the presence of xanthines. J Chromatogr 1992; 582: 181-187
• 12 Srinivasu P, Subbarao DV, Vegesna RV et al. A validated stability-indicating LC method for acetazolamide in the presence of degradation products and its process-related impurities. J Pharm Biomed Anal 2010; 52: 142-148
• 13 Gomaa ZS. Determination of acetazolamide in dosage forms by high performance liquid chromatography. Biomed Chromatogr 1993; 7: 134-135
• 14 Deventer K, Delbeke FT, Roels K et al. Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography-tandem mass spectrometry. Biomed Chromatogr 2002; 16: 529-535
• 15 Thörngren JO, Ostervall F, Garle M et al. A high-throughput multicomponent screening method for diuretics, masking a gents, central nervous system (CNS) stimulants and opiates in human urine by UPLC-MS/MS. J Mass Spectrom 2008; 43: 980-992
• 16 Thieme D, Grosse J, Lang R et al. Screening, confirmation and quantitation of diuretics in urine for doping control analysis by high-performance liquid chromatography-atmospheric pressure ionisation tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 2001; 757: 49-57
• 17 Politi L, Morini L, Polettini A et al. A direct screening procedure for diuretics in human urine by liquid chromatography-tandem mass spectrometry with information dependent acquisition. Clin Chim Acta 2007; 386: 46-52
• 18 Bogusz MJ, Hassan H, Al-Enazi E et al. Application of LC-ESI-MS-MS for detection of synthetic adulterants in herbal remedies. J Pharm Biomed Anal 2006; 41: 554-564
• 19 Goebel C, Trout GJ, Kazlauskas R. Rapid screening method for diuretics in doping control using automated solid phase extraction and liquid chromatography-electrospray tandem mass spectrometry. Analytica Chimca Acta 2004; 502: 65-74
• 20 Mazzarino M, de la Torre X, Botrè F. A screening method for the simultaneous detection of glucocorticoids, diuretics, stimulants, anti-oestrogens, beta-adrenergic drugs and anabolic steroids in human urine by LC-ESI-MS/MS. Anal Bioanal Chem 2008; 392: 681-698
• 21 US Food and Drug Administration. Guidance for industry: bioanalytical method validation. 2001 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070107.pdf