Simultaneous LC-MS-MS Determination of Lopinavir and Rifabutin in Human Plasma.
Tuberculosis (TB) with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome represents the most common infectious diseases worldwide. Anti-TB drugs are used concurrently with antiretroviral drug for treatment of TB-HIV co-morbidities. Due to lower risk of interaction with protease inhibitors, rifabutin is preferred over rifampicin in treatment of HIV and TB co-morbidity. A simple and specific liquid chromatography tandem mass spectrometry method was developed for quantification of rifabutin (RBT) and lopinavir (LPV) simultaneously in human plasma. Following extraction using 60% n-hexane in ethyl acetate, the processed samples were chromatographed on a Discovery HS C18 column (5 μm, 50 × 4.6 mm, id) using mobile phase [85% acetonitrile in ammonium acetate buffer (10 mM, pH 4.5)] at a flow rate of 0.7 mL/min. Mass spectrometric detection was performed in positive electrospray ionization mode using multiple reaction monitoring (RBT, m/z 847.7 → 815.4; LPV, m/z 629.6 → 447.4). Raloxifene and phenacetin were used as internal standards for RBT and LPV, respectively. Linearity was established in the range of 1-1,000 ng/mL and 0.5-10 µg/mL (R2 ≥ 0.99) for RBT and LPV, respectively. The recovery of LPV and RBT were always >90 and >50%, respectively. The precisions and accuracies were well within the acceptable limits of variation.
Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.|Academy of Scientific and Innovative Research, Mathura Road, New Delhi 110 025, India.
Swati
S
Jaiswal
Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.|Academy of Scientific and Innovative Research, Mathura Road, New Delhi 110 025, India.
Abhisheak
A
Sharma
Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.|Academy of Scientific and Innovative Research, Mathura Road, New Delhi 110 025, India.
Mahendra
M
Shukla
Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.|Academy of Scientific and Innovative Research, Mathura Road, New Delhi 110 025, India.
Jawahar
J
Lal
D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D061466:Lopinavir / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D017828:Rifabutin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D017828:Rifabutin; D061466:Lopinavir