Sensitive, selective and rapid determination of bupropion and its major active metabolite, hydroxybupropion, in human plasma by LC‐MS/MS: application to a bioequivalence study in healthy Indian subjects

Abstract

A sensitive, selective and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of bupropion (BUP) and its major active metabolite hydroxybupropion (HBUP) in human plasma. Separation of both the analytes and venlafaxine as internal standard (IS) from 50 μL human plasma was carried out by solid-phase extraction. The chromatographic separation of the analytes was achieved on a Zorbax Eclipse XDB C(18) (150 × 4.6 mm, 5 µm) analytical column using isocratic mobile phase consisting of 20 mm ammonium acetate-methanol (10:90, v/v), with a resolution factor of 3.5. The method was validated over a wide dynamic concentration range of 0.1-350 ng/mL for BUP and 0.1-600 ng/mL for HBUP. The matrix effect was assessed by post-column infusion and the mean process efficiency was 96.08 and 94.40% for BUP and HBUP, respectively. The method was successfully applied to a bioequivalence study of 150 mg BUP (test and reference) extended release tablet formulation in 12 healthy Indian male subjects under fed conditions.

Determination and validation of psammaplin A and its derivatives in rat plasma by liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic study

“…It strongly suggested that the fragmentation occurred by the cleavage of the disulfide bond, which gives ananalytically useful insight that other PsA derivatives with the disulfide bond may also have similar fragmentation patterns. The product ion of IS showed the m/z value of 184.2, which was consistent with the previous report [32].…”

“…Compared to studies by Kim et al [32] which reported the analysis of PsA alone using piroxicam as the internal standard for a pharmacokinetic study in mice, simultaneous determination of all three new analogues was possible with optimized mobile phase condition and run time using bupropion hydrochloride as internal standard. Moreover, the method was validated in terms of selectivity, linearity, accuracy, precision, and stability for benchtop stability as well as freeze-thaw stability for the first time.…”

Simultaneous quantitative determination of bupropion and its three major metabolites in human umbilical cord plasma and placental tissue using high-performance liquid chromatography–tandem mass spectrometry

“…The extraction methods of BUP and its metabolites from biological matrix include liquid-liquid extraction (LLE) [16–18], solid phase extraction (SPE) [11, 14, 19] and protein precipitation (PP) [12,22]. In this investigation, LLE and PP methods were used.…”

“…Analytical methods using liquid chromatography for separation of the drug and metabolites and detection by UV (LC-UV) at 254 nm (for bupropion) and 214 nm (for its metabolites), mass spectrometry (LC-MS) or LC-MS/MS have been developed and validated for quantitative determination of BUP and its major metabolite OH-BUP in human plasma [11,12,13,14,15] and urine [14]. Simultaneous quantitative determination of BUP and all metabolites in plasma using LC-MS/MS method coupled with monolithic column [16] or LC-UV [17,18], and in whole blood using ultra-LC-MS/MS [19] have been also reported.…”

MSn, LC‐MS‐TOF and LC‐PDA studies for identification of new degradation impurities of bupropion

“…(Fig. ) Several spectroscopic and chromatographic methods have been reported for the determination of bupropion alone (Al‐khamis, ), with its metabolites in plasma of human, rat or mouse (Borges et al ., ; Cooper et al ., ; Laizure and Devane, ; Loboz et al ., ; Parekh et al ., ; Yenicelli and Dogrukol, ; Zhang et al ., ), in urine (Coles and Kharasch, ), in whole blood (Denooz et al ., ) and in human umbilical cord plasma (Wang et al ., ). O'Byrne et al .…”