BACKGROUND: Nitazoxanide (NTZ) is used for the treatment of gastrointestinal tract colonization by anaerobic bacteria, viruses and other pathogens that represent a major cause of morbidity in Latin America. The aim of the present work was to develop and validate a UPLC-MS/MS method for the selective quantification of tizoxanide (TZN, the major metabolite of NTZ) in human plasma using niclosamide as internal standard; and examine its pharmacokinetic application in healthy volunteers. Nine male subjects received a single oral dose of a NTZ 500-mg tablet under fasting conditions. RESULTS: The method was linear between 0.1 and 10 µg/ml and capable of separating signals from free-TZN and those delivered by in-source collision-induced dissociation of TZN-glucuronide, quantifying it with accuracy and precision. Mean maximum plasma concentration was 6.79 µg/ml and was reached at 2.4 h post-dose. CONCLUSION: The method was validated, fulfilling regulatory guidelines. Results suggest low pharmacokinetic variability in the assayed population.
BACKGROUND:Nitazoxanide (NTZ) is used for the treatment of gastrointestinal tract colonization by anaerobic bacteria, viruses and other pathogens that represent a major cause of morbidity in Latin America. The aim of the present work was to develop and validate a UPLC-MS/MS method for the selective quantification of tizoxanide (TZN, the major metabolite of NTZ) in human plasma using niclosamide as internal standard; and examine its pharmacokinetic application in healthy volunteers. Nine male subjects received a single oral dose of a NTZ 500-mg tablet under fasting conditions. RESULTS: The method was linear between 0.1 and 10 µg/ml and capable of separating signals from free-TZN and those delivered by in-source collision-induced dissociation of TZN-glucuronide, quantifying it with accuracy and precision. Mean maximum plasma concentration was 6.79 µg/ml and was reached at 2.4 h post-dose. CONCLUSION: The method was validated, fulfilling regulatory guidelines. Results suggest low pharmacokinetic variability in the assayed population.
Authors: Michael T Schweizer; Kathleen Haugk; Jožefa S McKiernan; Roman Gulati; Heather H Cheng; Jessica L Maes; Ruth F Dumpit; Peter S Nelson; Bruce Montgomery; Jeannine S McCune; Stephen R Plymate; Evan Y Yu Journal: PLoS One Date: 2018-06-01 Impact factor: 3.240
Authors: Rajith K R Rajoli; Henry Pertinez; Usman Arshad; Helen Box; Lee Tatham; Paul Curley; Megan Neary; Joanne Sharp; Neill J Liptrott; Anthony Valentijn; Christopher David; Steven P Rannard; Ghaith Aljayyoussi; Shaun H Pennington; Andrew Hill; Marta Boffito; Steve A Ward; Saye H Khoo; Patrick G Bray; Paul M O'Neill; W David Hong; Giancarlo A Biagini; Andrew Owen Journal: Br J Clin Pharmacol Date: 2020-12-01 Impact factor: 4.335