Quantification of Iohexol in Serum by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Vicente, Faye B.; Vespa, Gina; Miller, Alan L.; Haymond, Shannon

doi:10.1007/978-1-4939-3252-8_20

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…Few studies have compared these two methods for GFR measurement purposes [ 69 ], yet these data indicate that the performance of XRF is inferior to HPLC-UV due to its lower sensitivity [ 69 , 73 ]. Measurement of iohexol by LC-MS/MS has been more recently described by several authors [ 32 , 74 – 79 ]. LC-MS/MS is theoretically a more sensitive and specific method but is more complex and costly compared with HPLC-UV.…”

Section: Iohexol: Analytical and Other Metrics Considerationsmentioning

confidence: 99%

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

et al. 2016

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While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

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Section: Iohexol: Analytical and Other Metrics Considerationsmentioning

confidence: 99%

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

et al. 2016

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“…61 The method development was based on previously validated LC-MS/MS assays for these agents. 7,13,15,57,[62][63][64][65] 2.2 | Clinical validation study…”

Section: Bioanalytical Methods Development and Validationmentioning

confidence: 99%

“…A novel multianalyte LC–MS/MS assay capable of quantifying tacrolimus, everolimus, sirolimus, cyclosporine, MPA, creatinine and iohexol simultaneously in DBS and VAMS samples was developed as per the European Medicines Agency guideline on bioanalytical method validation 61 . The method development was based on previously validated LC–MS/MS assays for these agents 7,13,15,57,62–65 …”

Section: Methodsmentioning

confidence: 99%

Volumetric microsampling for simultaneous remote immunosuppressant and kidney function monitoring in outpatient kidney transplant recipients

Zwart

Metscher

Boog

et al. 2022

Brit J Clinical Pharma

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Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden as compared to conventional venous sampling at the clinic. We developed a liquid chromatography-tandem mass spectrometry assay to quantify tacrolimus, mycophenolic acid (MPA), creatinine and iohexol in dried blood spot (DBS), and volumetric absorptive microsample (VAMS) samples. Methods:The assay was successfully validated analytically for all analytes. Clinical validation was conducted by direct comparison of paired DBS, VAMS and venous reference samples from 25 kidney transplant recipients. Patients received iohexol 5-15 minutes before immunosuppressant intake and were sampled 0, 1, 2 and 3 hours thereafter, enabling tacrolimus and MPA area under the concentration-time curve (AUC) and creatinine-based and iohexol-based glomerular filtration rate (GFR) estimation. Method agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and the percentages of values within 15-30% of the reference (P 15 -P 30 ) with a P 20 acceptance threshold of 80%.Results: For DBS samples, method agreement was excellent for tacrolimus trough concentrations (n = 25, P 15 = 92.0%) and AUCs (n = 25; P 20 = 95.8%) and adequate for creatinine-based GFR trend monitoring (n = 25; P 20 = 80%). DBS-based MPA AUC assessment showed suboptimal agreement (n = 16; P 20 = 68.8%), but was considered acceptable given its P 30 of 100%. The assay performed inadequately for DBS-based iohexol GFR determination (n = 24; P 20 = 75%). The VAMS technique generally showed inferior performance, but can be considered for certain situations. Conclusion:The assay was successfully validated for tacrolimus, MPA and creatinine quantification in DBS samples, enabling simultaneous remote kidney function trendThe authors confirm that the Principal Investigator for this article is Dirk Jan Moes.

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“…39 Analytical measurement of iohexol has been performed using a variety of measurement procedures including X-ray fluorescence, 63,66 HPLC-UV, 65,67,68 and LC-MS/MS. 59,69,70 It is important to note that iohexol exists in different isomeric forms which have low energy of activation and slowly interconvert in aqueous solution. Thus, when placing crystalline iohexol into solution, one must allow sufficient time for equilibration, since the ratio of the endo-and exoisoforms could change from the initial state.…”

Section: Iohexolmentioning

confidence: 99%

Challenges in Measuring Glomerular Filtration Rate: A Clinical Laboratory Perspective

Seegmiller

Eckfeldt

Lieske

2018

Advances in Chronic Kidney Disease

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The assessment of kidney function is a cornerstone in the clinical management and health of the patient. Although the kidneys perform many physiologic functions and are essential for maintaining homeostasis, kidney function is typically evaluated, quantitated, and understood using the glomerular filtration rate (GFR). Although GFR can be directly measured using a variety of externally administered glomerular filtration markers, in general practice, the GFR is usually estimated (eGFR) using endogenous markers that are cleared primarily by kidney filtration. Common situations exist where the GFR needs to be measured (mGFR) in order to proceed with care. This manuscript will review laboratory challenges in the assessment of GFR. Key points to consider when implementing a mGFR testing protocol are the following: marker selection, clearance methodology (urinary vs solely plasma measurements of filtration marker), sample collection, number of samples to collect, staff required, and analytical measurement technology for the filtration marker selected. We suggest those wanting to implement mGFR testing examine site-specific institutional resources along with patient population and proceed with the approaches best suited for their clinical needs and laboratory resources available.

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Quantification of Iohexol in Serum by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Cited by 7 publications

References 6 publications

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

Volumetric microsampling for simultaneous remote immunosuppressant and kidney function monitoring in outpatient kidney transplant recipients

Challenges in Measuring Glomerular Filtration Rate: A Clinical Laboratory Perspective

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