Determination of lansoprazole, 5-hydroxylansoprazole, and lansoprazole sulfone in human plasma for CYP2C19 and CYP3A4 phenotyping
- 51 Downloads
A simple and sensitive liquid chromatography method with absorbance or mass spectrometry detection was developed and validated for the determination of lansoprazole, lansoprazole sulfone, and 5-hydroxylansorpazole in human serum with omeprazole as an internal standard. Analytes were, after an extraction step with a mixture of isopropyl alcohol: dichloromethane (2:8, v/v), separated in a gradient elution (acetonitrile: 20 mM ammonium formate) and detected at 280 and 300 nm or by monitoring selective reactions in a triple quadrupole mass analyzer. The limits of detection were, for all analytes, below 2 ng/mL and 3 pg/mL in the LC UV and LC MS method, respectively. The combined linear dynamic range exceeded 5 orders of magnitude. The method was successfully applied in the assessment of CYP2C19 and CYP3A4 metabolic phenotypes in ST-elevated myocardial infarction patients receiving novel anticoagulant treatment.
KeywordsCytochrome P450 Phenotype Lansoprazole 5-Hydroxylansoprazole Lansoprazole sulfone Liquid chromatography Mass spectrometry Metabolites
This work was supported by funds from the Faculty of Medicine MU to a junior researcher Ondřej Peš and by the Specific University Research Grant (MUNI/A/1132/2017, MUNI/A/0910/2017) provided by the Ministry of Education, Youth and Sports of the Czech Republic and by the project no. LQ1605 from the National Program of Sustainability II (MEYS CR).
Compliance with ethical standards
Conflict of interest
Authors declare there are no potential conflicts of interest to disclose.
- Belal F, El-Enany N, Rizk M (2004) Anodic polarographic determination of lansoprazole and omeprazole in pure form and in pharmaceutical dosage forms. J Food Drug Anal 12:102–109Google Scholar
- Bharathi DV, Hotha KK, Jagadeesh B, Chatki PK, Thriveni K, Mullangi R, Naidu A (2009) Simultaneous estimation of four proton pump inhibitors–lansoprazole, omeprazole, pantoprazole and rabeprazole: development of a novel generic HPLC-UV method and its application to clinical pharmacokinetic study. Biomed Chromatogr 23:732–739CrossRefGoogle Scholar
- Dierks EA, Stams KR, Lim HK, Cornelius G, Zhang HL, Ball SE (2001) A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450 s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. Drug Metab Dispos 29:23–29Google Scholar
- Dynamed American Society of Health System Pharmacists, I, 1995–2018 (2018) Dynamed. EBSCO Information Services, IpswichGoogle Scholar
- FDA (2018) Bioanalytical method validation, guidance for industry. In: U.S. Department of Health and Human Services, F. A. D. A., Center for Drug Evaluation and Research (CDER) (Ed.). FDA, p 44Google Scholar
- Medicines and Healthcare Regulatory Agency (MHRA) (2017) SmPC, Zoton FasTab. In: MHRA (ed), pp 1–14Google Scholar
- Sun L, Cao Y, Jiao H, Fang Y, Yang Z, Bian M, Zhang H, Gong X, Wang Y (2015) Enantioselective determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study. J Sep Sci 38:3696–3703CrossRefGoogle Scholar
- Uno T, Yasui-Furukori N, Takahata T, Sugawara K, Tateishi T (2005a) Determination of lansoprazole and two of its metabolites by liquid-liquid extraction and automated column-switching high-performance liquid chromatography: application to measuring CYP2C19 activity. J Chromatogr B Anal Technol Biomed Life Sci 816:309–314CrossRefGoogle Scholar
- Uno T, Yasui-Furukori N, Takahata T, Sugawara K, Tateishi T (2005b) Determination of lansoprazole and two of its metabolites by liquid-liquid extraction and automated column-switching high-performance liquid chromatography: application to measuring CYP2C19 activity. J Chromatogr B Analyt Technol Biomed Life Sci 816:309–314CrossRefGoogle Scholar
- Yang DZ, Gao YY, Jiang XL, Dong WF, Tang DQ (2011) Pharmacokinetics of Lansoprazole Injection in Peptic Ulcer and Healthy Volunteers. Lat Am J Pharm 30:1016–1020Google Scholar
- Zhang H, Xia CH, Huang SB, Liu MY, Xiong YQ (2014) Determination of Lansoprazole in Human Plasma Using LC-MS and Pharmacokinetic Study in Chinese Healthy Volunteers. Lat Am J Pharm 33:624–630Google Scholar