Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study.
Article Details
- CitationCopy to clipboard
Thappali SR, Varanasi KV, Veeraraghavan S, Vakkalanka SK, Mukkanti K
Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study.
J Mass Spectrom. 2012 Dec;47(12):1612-9. doi: 10.1002/jms.3103.
- PubMed ID
- 23280750 [ View in PubMed]
- Abstract
A sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) was developed and validated for simultaneous quantification IC87114, roflumilast (RFM), and its active metabolite roflumilast N-oxide (RFN) using tolbutamide as an internal standard. The analytes were extracted by using liquid-liquid extraction and separated on a reverse phase C(18) column (50 mm x 3 mm i.d., 4.6 micro) using methanol: 2 mM ammonium acetate buffer, pH 4.0 as mobile phase at a flow rate 1 mL/min in gradient mode. Selective reaction monitoring was performed using the transitions m/z 398.3 > 145.9, 403.1 >186.9, 419.1 > 187.0 and 271.1 > 155.0 to quantify quantification IC87114, RFM, RFN and tolbutamide, respectively. The method was validated over the concentration range of 0.1-60 ng.mL(-1) for RFM and RFN and 6 to 2980 ng.mL(-1) for IC87114. Intra- and inter-day accuracy and precision of validated method were within the acceptable limits of <15% at all concentrations. Coefficients of correlation (r(2) ) for the calibration curves were >0.99 for all analytes. The quantitation method was successfully applied for simultaneous estimation of IC87114, RFM and RFN in a pharmacokinetic drug-drug interaction study in Wistar rats.
DrugBank Data that Cites this Article
- Drugs