A validated LC-MS/MS method for the estimation of glimepiride and pitavastatin in rat plasma: Application to drug interaction studies.
Glimepiride (GLI) is prescribed for the management of type-2 diabetes where as pitavastatin (PIT) for the treatment of diabetes associated dyslipidemia. Both the drugs are metabolized by CYP2C9 and have the potential of altering the enzyme through either inhibition or induction. In this respect, we present a simple, fast and validated bioanalytical LC-MS/MS method for the simultaneous estimation of GLI and PIT from rat plasma. Waters XTerra RP HPLC column (4.6×100mm, 5μm) with mobile phase consisting of acetonitrile and 10mM ammonium acetate (pH-6.0) in the ratio 85:15 (v/v) at a flow rate of 1mL/min was used for the chromatographic separation. The negative ionization mode with MRM transitions: m/z 420.17→288.13 for PIT, m/z 489.59→350.12 for GLI and m/z 380.08→316.31for celecoxib as internal standard (IS). A total run time of 3min and LLOQ was found to be 5ng/mL for both PIT and GLI. The method was applied to study the drug interaction between GLI and PIT in rat liver microsomes. In vivo rat pharmacokinetics study showed there was a 1.29-fold increase in AUC0-∞and 1.2-fold decrease in the clearance of PIT in presence of GLI. No notable difference in the pharmacokinetic profile of GLI was observed upon the intravenous co-administration of PIT.
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana 500037, India.
Shruti
S
Surendran
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana 500037, India.
David
D
Paul
Drug Metabolism and Pharmacokinetic Department, Aurigene Discovery Technologies Limited, Bollaram Road, Miyapur, Hyderabad 500049, Telangana, India.
Ratna
R
Sushmita
Drug Metabolism and Pharmacokinetic Department, Aurigene Discovery Technologies Limited, Bollaram Road, Miyapur, Hyderabad 500049, Telangana, India.
Lavanya
L
Krishna
Drug Metabolism and Pharmacokinetic Department, Aurigene Discovery Technologies Limited, Bollaram Road, Miyapur, Hyderabad 500049, Telangana, India.
Nirbhay Kumar
NK
Tiwari
Drug Metabolism and Pharmacokinetic Department, Aurigene Discovery Technologies Limited, Bollaram Road, Miyapur, Hyderabad 500049, Telangana, India. Electronic address: sanjeev_g@aurigene.com.
Sanjeev
S
Giri
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana 500037, India. Electronic address: satish.niperhyd@gov.in.
Nanjappan
N
Satheeshkumar
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004347:Drug Interactions; D005260:Female; D016014:Linear Models; D008862:Microsomes, Liver; D011804:Quinolines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013453:Sulfonylurea Compounds / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
D011804:Quinolines; D013453:Sulfonylurea Compounds; C057619:glimepiride; C108475:pitavastatin
Drug interaction; Glimepiride; LC–MS/MS; Pitavastatin; Rat liver microsomes