scholarly journals Clinical Mass Spectrometry Discovered Human IgG Sialylation as a Potential Biosignature for Kidney Function

2021 ◽  
Vol 11 (8) ◽  
pp. 761
Author(s):  
Chih-Chin Kao ◽  
San-Yuan Wang ◽  
Yung-Kun Chuang ◽  
Wei-Yuan Lee ◽  
Wei-Chiao Chang ◽  
...  

Immunoglobulin G (IgG) N-glycosylation was discovered to have an association with inflammation status, which has the potential to be a novel biomarker for kidney diseases. In this study, we applied an ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to plasma and urine samples from 57 individuals with different levels of kidney function. Natural abundances of total IgG, IgG1, IgG2, and IgG3 subclasses in plasma showed positive correlations to the estimated glomerular filtration rates (eGFRs). Eighteen IgG glycopeptides also showed positive correlations. In contrast, higher IgG amounts were found in urine samples from participants with lower eGFR values. After normalizing IgG glycopeptides from plasma to their respective protein amounts, H4N4F1S1-IgG1 (r = 0.37, p = 0.0047, significant) and H5N4F1S1-IgG1 (r = 0.25, p = 0.063, marginally significant) were the two glycopeptides that still had positive correlations with eGFRs. The results showed that the UHPLC-MS/MS method is capable of investigating IgG profiles, and monitoring IgG and glycosylation patterns is worthy of further clinical application for kidney disease.

Author(s):  
Genquan Yan ◽  
Lu Yu ◽  
Xu Chen ◽  
Triet Tran ◽  
Lam Nguyen ◽  
...  

AbstractA rapid and sensitive High-Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC/MS/MS) method for determining apremilast in beagle dog plasma and urine samples was developed and validated using clopidogrel as the internal standard (IS). Apremilast was extracted from the plasma and urine samples by liquid–liquid extraction using methyl tert-butyl ether. Chromatographic separation was performed using a C8 column with gradient elution and a mobile phase containing methanol and 0.1% formic acid. Quantification was achieved in multiple reaction monitoring (MRM) mode with a transition of m/z 461.3→178.2 for apremilast and m/z 322.2→184.1 for clopidogrel (IS). This method was validated regarding its specificity, linearity, precision, accuracy, and stability. The lower limit of quantification (LLOQ) for this method was 5 ng/mL, and the calibration curve was linear over 5–1,000 ng/mL. The intra- and inter-run coefficients of variance (CV) of aprelimast in plasma samples were less than 12.92% and 10.64%, respectively, while in urine samples, the CV were less than 11.84% and 10.20%, respectively. The samples were stable under the tested conditions. This method was successfully applied to a pharmacokinetic study in beagle dogs following oral administration of 10 mg of apremilast.


2002 ◽  
Vol 48 (2) ◽  
pp. 301-306 ◽  
Author(s):  
Gisela Skopp ◽  
Lucia Pötsch

Abstract Background: Unconjugated 11-nor-Δ9-carboxy-tetrahydrocannabinol (THCCOOH) in blood and urine has been proposed as a valuable marker, but the glucuronide (THCCOOglu) is present in considerably higher concentrations than the parent drug. Acyl glucuronides have been shown to be potentially reactive conjugates, which may affect the in vitro metabolite pattern. Methods: Extraction procedures and a liquid chromatography-tandem mass spectrometry assay were developed and validated to investigate the stability of THCCOOglu in urine and plasma. Plasma and urine samples with added THCCOOglu were stored at −20, 4, 20, and 40 °C up to 10 days. Results: The glucuronide was stable at −20 °C in both matrices, whereas THCCOOglu concentrations decreased at all other storage conditions. For a given storage time and temperature, the decrease in plasma was higher than that in urine. At 20 °C, a marked change in concentration could be observed within 2 days of storage. Degradation of THCCOOglu followed an apparent first-order process and led to the formation of THCCOOH. The sum of the molar concentrations of both analytes corresponded only to the initial THCCOOglu in plasma and urine samples stored at 4 °C. Conclusions: The in vitro degradation of THCCOOglu prevents clinical conclusions based on the metabolite pattern or the concentration of unconjugated THCCOOH in samples stored at ≥4 °C for prolonged periods.


2007 ◽  
Vol 177 (4S) ◽  
pp. 295-295
Author(s):  
Michael Mullerad ◽  
Haleem J. Issaq ◽  
Alexander Kravtsov ◽  
Timothy Waybright ◽  
Brian Luke ◽  
...  

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