Gradient elution mode for the troubleshooting of matrix effect on the determination of G004 in different tissues by LC‐MS/MS

Abstract

A steep gradient elution mode was applied to reduce the risk of matrix effect (ME) for the determination of G004, a novel sulfonylurea hypoglycemic drug, in a tissue distribution study by LC-MS/MS. The mass spectra of the total-ion-current chromatograms combined with the post-column infusion traces enabled the 'unseen' interfering species to be directly detected, and ensured that the chromatography conditions and sample preparation method were adequate to overcome the ME. According to this, a steep gradient elution mode was designed to overcome the intense ME from different tissues. The analysis was performed by monitoring the transitions m/z 558.1 → 419.0 for G004 and m/z 489.3 → 364.1 for glimepiride used as the internal standard. Calibration curves recovered over a range from 0.1 to 10000 ng/mL for seven different tissues. Sex-related difference was found in the tissue distribution. The drug levels in the tissues of female rats were about two to three times higher than those in male counterparts. The highest level was observed in liver, then in kidney, heart, pancreas, lung and spleen, but no G004 was detected in brain. G004 was slowly eliminated from female rats compared with male rats. There was no long-term accumulation of G004 in male or female rat tissues.

Simultaneous Determination of Urine Methotrexate, 7-Hydroxy Methotrexate, Deoxyaminopteroic Acid, and 7-Hydroxy Deoxyaminopteroic Acid by UHPLC-MS/MS in Patients Receiving High-dose Methotrexate Therapy

“…30 The matrix effects of both 7-OH MTX and 7-OH DAMPA might be well compensated by using an efficient sample purification technology such as solid phase extraction, an efficient separation procedure, and/or the isotope internal standards. [29][30][31] All analytes were stable in urine and post-extracted urine matrix under tested conditions, which was consistent with the results in previous studies. 2, 3, 15-17, 21, 23, 24…”

“…18,20 The recovery and matrix factor of analytes were comparable to the observations in published studies in various biological fluids including human urine, plasma, serum, and cerebrospinal fluid (recovery: 72% to 126% for MTX, 67% to 122% for 7-OH MTX, and 54.4% to 105.1% for DAMPA; matrix factor: 70.5% to 118% for MTX, 90% to 105% for 7-OH MTX, and 101% to107% for DAMPA). 2, 3, 15-18, 23, 24, 26 The possible reasons for the matrix induced response enhancement for both 7-OH MTX (117.65% to 124.70%) and 7-OH DAMPA (156.57% to 172.93%), and the big inter-individual variance of 7-OH DAMPA matrix factor (CV < 20.68%) were summarized as follows: (1) the one-step protein precipitation for sample extraction retained Analytical Sciences many matrix in the post-extracted samples; 29,30 (2) the fast separation procedure of the HPLC method could not efficiently separate all of the matrix from the analytes; 30,31 (3) MTX-D and DAMPA-D were used for the quantitation of 7-OH MTX and 7-OH DAMPA, respectively. However, the chemical structures and retention times were different between the two internal standards and the two analytes, therefore their matrix effects could not be well compensated.…”

Development and validation of an LC‐MS/MS method for the determination of tigecycline in human plasma and cerebrospinal fluid and its application to a pharmacokinetic study

“…Recovery and matrix effect can significantly affect the accuracy of the LC‐MS/MS method and should be evaluated (European Medicines Agency, ; US Food and Drug Administration et al ., ; Hu et al, ; Patel, Suhagia, Jangid, Mistri, & Desai, ). For this study three QC levels (50, 400, 1500 ng/mL for plasma and 750, 7500, 75,000 ng/mL for CSF) were used to evaluate the matrix effect and recovery.…”

Matrix effects demystified: Strategies for resolving challenges in analytical separations of complex samples

“…A contribution to ME may result from the use of nominal isobars of the target analytes during ionization, which can be detected and avoided using highresolution MS, as reported by Reyes-Garcés et al [96]. In addition, isotopically labeled internal standards, sample dilutions, and steeper elution gradients which can quickly eliminate ME-associated interferences in LC, especially for lipids, can be employed to minimize matrix interference [97]. Finally, SPME stands out as a nonexhaustive technique, ensuring minimal disturbances to binding equilibria compared to other exhaustive techniques.…”

“…[96]. In addition, isotopically labeled internal standards, sample dilutions, and steeper elution gradients which can quickly eliminate ME‐associated interferences in LC, especially for lipids, can be employed to minimize matrix interference [97]. Finally, SPME stands out as a non‐exhaustive technique, ensuring minimal disturbances to binding equilibria compared to other exhaustive techniques.…”