A single LC-tandem mass spectrometry method for the simultaneous determination of four H2 antagonists in human plasma.
A sensitive and universal LC-MS/MS method for the simultaneous determination of famotidine, cimetidine, ranitidine and lafutidine in human plasma was presented. This is the first single LC-MS/MS method reported for the simultaneous analysis of these four H(2) antagonists in human plasma. Following liquid-liquid extraction with ethyl acetate, the separation was performed on an Agilent Zorbax SB-CN (150 mm x 2.1mm I.D., 5 microm) column using a mobile phase consisted of methanol:20 mM ammonium acetate (55:45, v/v). The total run time was 7 min per sample. Quantification was performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring (SRM) detection in the positive mode. All calibration curves showed good linear regression (r(2)>0.99) from 0.5 to 1000 ng/mL for famotidine and lafutidine, and 5-20,000 ng/mL for cimetidine and ranitidine. The method showed good precision and accuracy with overall intra- and inter-day variations of 1.37-9.29% and 3.51-9.40%, respectively. The assay was successfully applied to a bioequivalence study using ranitidine as the model compound.
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.
Xiuhong
X
Sun
Yuan
Y
Tian
Zunjian
Z
Zhang
Yun
Y
Chen
D000081:Acetamides / Q000097:blood; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D002927:Cimetidine / Q000097:blood; D015738:Famotidine / Q000097:blood; D006635:Histamine H2 Antagonists / Q000097:blood*; D006801:Humans; D010880:Piperidines / Q000097:blood; D011725:Pyridines / Q000097:blood; D011899:Ranitidine / Q000097:blood; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
D000081:Acetamides; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine