Validation of an LC/MS method for the determination of gemfibrozil in human plasma and its application to a pharmacokinetic study

Abstract

Gemfibrozil, a fibric acid hypolipidemic agent, is increasingly being used in clinical drug-drug interaction studies as an inhibitor of drug metabolizing enzymes and drug transporters. The validation of a fast, accurate, and precise LC/MS method is described for the quantitative determination of gemfibrozil in an EDTA-anticoagulated human plasma matrix. Briefly, gemfibrozil was extracted from human plasma by an acetonitrile protein precipitation method. The assay was reproducible with intra-assay precision between 1.6% and 10.7%, and inter-assay precision ranging from 4.4% to 7.8%. The assay also showed good accuracy, with intra-assay concentrations within 85.6% and 108.7% of the expected value, and inter-assay concentrations within 89.4 to 104.0% of the expected value. The linear concentration range was between 0.5 and 50 μg/mL with a lower limit of quantitation of 0.5 μg/mL when 125 μL of plasma were extracted. This LC/MS method yielded a quick, simple, and reliable protocol for determining gemfibrozil concentrations in plasma and is applicable to clinical pharmacokinetic studies.

Optimization of chromatography to overcome matrix effect for reliable estimation of four small molecular drugs from biological fluids using LC–MS/MS

“…Further, fine tuning of the cone voltage, which controls the entry of the ions into the ion block, and collision energy, which promotes formation of fragment in the collision cell, was carried out to ensure adequate intensity of the selected MRM transitions. The fragmentation patterns for all of the drugs were in reasonable agreement with those reported in literature for GEM (Borges et al, ), RIV (Arvand & Fallahi, ; Rower et al, ), TEL (Bhatt et al, ; Mirparizi et al, ) and TAC (Brown et al, ; De Nicolò et al, ).…”

“…The fragmentation patterns for all of the drugs were in reasonable agreement with those reported in literature for GEM (Borges et al, 2005), RIV (Arvand & Fallahi, 2013;Rower et al, 2010), TEL (Bhatt et al, 2007;Mirparizi et al, 2018) and TAC (Brown et al, 2005;De Nicolò et al, 2016).…”

“…GEM, RIV and TEL have been analyzed in human plasma as single analytes, along with their metabolites and in combination with other drugs, while TAC has been analyzed in whole blood samples as it gets sequestered within the erythrocytes. GEM has been determined using high-performance liquid chromatography (HPLC) with ultraviolet (UV) (Panahi, Feizbakhsh, Karimpour, & Moniri, 2013;Su et al, 2010;Vittal et al, 2006), fluorescence (González-Peñas et al, 2001;Kang, Wang, Xie, & Li, 2009;Kim et al, 2006) and mass spectrometry (MS) detection (Borges et al, 2005;Rower, Bushman, Hammond, Kadam, & Aquilante, 2010). For RIV, several analytical techniques such as voltammetry (Arvand & Fallahi, 2013), capillary electrophoresis (Nicolaou & Kapnissi-Christodoulou, 2012), micellar electrokinetic chromatography (Hsieh, Yang, Yeh, Lin, & Chen, 2009), HPLC-UV (Amini & Ahmadiani, 2010;Mirparizi, Rajabi, & Asghari, 2018) and LC-MS/MS (Bhatt et al, 2007;Frankfort et al, 2006;Pommier & Frigola, 2003;Trivedi, Upadhyay, Yadav, Shrivastav, & Sanyal, 2014) have been used for its estimation in human plasma.…”

In vivo pharmacological evaluation of a lactose-conjugated luteinizing hormone releasing hormone analogue

“…The developed method in this study was capable of detecting the compound over a range of 0.01 to 20 µg/ml with a detection limit of 0.01 µg/ml. The precision and accuracy of the method was assessed by performing intra-and inter-day assays The precision value obtained was below 12% for the four QC levels which was in acceptable limit based on FDA guidelines (the precision value should not exceed 15%) (Rower et al, 2010). The high accuracy (98.2%…”

Study the pharmacokinetics of AV‐45 in rat plasma and metabolism in liver microsomes by ultra‐performance liquid chromatography with mass spectrometry

“…Bench‐top stability of extracted samples, room temperature stability, refrigerated stability of extracted sample at 4°C, freeze–thaw stability and long term stability at −20°C were performed at 5.00, 100 and 750 ng/mL using five replicates at each concentration. To meet the acceptance criteria the percentage bias should be within ±15% (Nirogi et al ., ; Rower et al ., ).…”