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Research Article

Development of an HPLC–MS/MS method to determine janagliflozin in human plasma and urine: application in clinical study

    Ling Song

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    Clinical Pharmacokinetics Laboratory, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, PR China

    ,
    Yang Liu

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    ,
    Xueting Yao

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    ,
    Hongzhong Liu

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    ,
    Bo Chen

    XuanZhu Pharma Co., Ltd., Jinan, Shandong, 250101, PR China

    ,
    Xifeng Ma

    XuanZhu Pharma Co., Ltd., Jinan, Shandong, 250101, PR China

    ,
    Huimin Zhou

    XuanZhu Pharma Co., Ltd., Jinan, Shandong, 250101, PR China

    ,
    Chengkon Shih

    XuanZhu Pharma Co., Ltd., Jinan, Shandong, 250101, PR China

    ,
    Ji Jiang

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    ,
    Xijing Chen

    *Author for correspondence:

    E-mail Address: 83271286@163.com

    Clinical Pharmacokinetics Laboratory, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, PR China

    ,
    Pei Hu

    **Author for correspondence:

    E-mail Address: hubei01_pumch@163.com

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    &
    Dongyang Liu

    ***Author for correspondence:

    E-mail Address: liudongyang@pumch.cn

    Clinical Pharmacology Research Center, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, PR China

    Published Online:https://doi.org/10.4155/bio-2018-0129

    Aim: Janagliflozin is a novel, orally selective sodium-glucose co-transporter-2 (SGLT2) inhibitor, which showed good efficacy and safety in preclinical study. The objective of this study is to develop and validate the HPLC–MS/MS method to determine janagliflozin in both of human urine and plasma. Methods: Janagliflozin was separated on Waters Xbridge Phenyl C18 column and detected on API 4000 tandem mass spectrometer with ESI source in negative mode. Results: This method provided good linearity in the range of 5–5000 ng/ml and 5–1000 ng/ml in plasma and urine. The matrix effect and extraction recoveries across three concentration levels were consistent. Conclusion: This validated method is reliable and has been successfully applied to a first-in-human trial of janagliflozin in Chinese subjects.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Upadhyay J, Polyzos SA, Perakakis N et al. Pharmacotherapy of Type 2 diabetes: an update. Metab. Clin. Exp. 78, 13–42 (2018).
    • 2 Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycemia in Type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38(1), 140–149 (2015).
    • 3 Marx N, Mcguire DK. Sodium-glucose cotransporter-2 inhibition for the reduction of cardiovascular events in high-risk patients with diabetes mellitus. Eur. Heart J. 37(42), 3192–3200 (2016).• A strong proof to support sodium-glucose co-transporter-2 inhibitor for the reduction of cardiovascular events in diabetes mellitus patients.
    • 4 Avranas K, Imprialos K, Stavropoulos K et al. Sodium-glucoser cotransporter 2 inhibitors: glucose lowering against other hypoglycemic agents. Cardiovasc. Hematol. Disord. Drug Targets 18(2), 94–103 (2018).
    • 5 Aubry AF, Gu H, Magnier R et al. Validated LC–MS/MS methods for the determination of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor in normal and ZDF rat plasma. Bioanalysis 2(12), 2001–2009 (2010).
    • 6 Dong ST, Niu HM, Wu Y et al. Plasma pharmacokinetic determination of canagliflozin and its metabolites in a Type 2 diabetic rat model by UPLC–MS/MS. Molecules 23(5), (2018).
    • 7 Iqbal M, Ezzeldin E, Al-Rashood KA, Asiri YA, Rezk NL. Rapid determination of janagliflozin in rat plasma by UHPLC–MS/MS using negative ionization mode to avoid adduct-ions formation. Talanta 132, 29–36 (2015).
    • 8 Ji QC, Xu X, Ma E et al. Selective reaction monitoring of negative electrospray ionization acetate adduct ions for the bioanalysis of dapagliflozin in clinical studies. Anal. Chem. 87(6), 3247–3254 (2015).
    • 9 Kobuchi S, Ito Y, Yano K, Sakaeda T. A quantitative LC–MS/MS method for determining ipragliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, and its application to a pharmacokinetic study in rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1000, 22–28 (2015).
    • 10 Kobuchi S, Matsuno M, Fukuda E, Ito Y, Sakaeda T. Development and validation of an LC–MS/MS method for the determination of tofogliflozin in plasma and its application to a pharmacokinetic study in rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1027, 227–233 (2016).
    • 11 Kobuchi S, Matsuno M, Kawamoto M et al. A simple and rapid LC–MS/MS method for quantitation of luseogliflozin in rat plasma and its application to a PK study. Bioanalysis 9(2), 163–171 (2017).
    • 12 Kobuchi S, Yano K, Ito Y, Sakaeda T. A validated LC–MS/MS method for the determination of janagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, in a lower volume of rat plasma: application to pharmacokinetic studies in rats. Biomed. Chromatogr. doi:10.1002/bmc.3720 (2016).
    • 13 US FDA. Guidance for Industry: Bioanalytical Method Validation (2001). http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf.
    • 14 China Food and Drug Administration (2015). http://www.sda.gov.cn/gsz05106/08.pdf.
    • 15 US FDA. Draft Guidance for Industry in Bioanalytical Method Validation (2013). https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm368107.pdf.
    • 16 Niessen WM. Fragmentation of toxicologically relevant drugs in negative-ion liquid chromatography–tandem mass spectrometry. Mass Spectrom. Rev. 31(6), 626–665 (2012).•• Excellent review summarized the drug fragmentation in ESI negative mode.
    • 17 Wang L, Duan C, Wu D, Guan Y. Quantification of endogenous brassinosteroids in sub-gram plant tissues by in-line matrix solid-phase dispersion–tandem solid phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. A 1359, 44–51 (2014).•• Excellent example for method development of bioanalytical assays using HPLC–MS/MS coupled with the solid-phase extraction procedure.
    • 18 Boyaci E, Rodriguez-Lafuente A, Gorynski K et al. Sample preparation with solid phase microextraction and exhaustive extraction approaches: Comparison for challenging cases. Anal. Chim. Acta 873, 14–30 (2015).•• Good summary about the main advantages and limitations of the different sample preparation approaches.
    • 19 Liu D, Ma X, Liu Y et al. Quantitative prediction of human pharmacokinetics and pharmacodynamics of imigliptin, a novel DPP-4 inhibitor, using allometric scaling, IVIVE and PK/PD modeling methods. Eur. J. Pharm. Sci. 89, 73–82 (2016).•• A good example to predict PK concentrations and to support the range setting of the bioanalytical methods.
    • 20 China Food and Drug Administration. Drug Clinical Trial Registration and Information Publicity Platform (CTR20170535) (May 31st 2017). http://www.chinadrugtrials.org.cn/eap/clinicaltrials.searchlistdetail.• The corresponding details of janagliflozin clinical single dose ascending trial.