Yıl: 2022 Cilt: 26 Sayı: 1 Sayfa Aralığı: 136 - 144 Metin Dili: İngilizce DOI: 10.29228/jrp.110 İndeks Tarihi: 17-06-2022

Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS

Öz:
Down syndrome is a common genetic disorder that results from the presence of an extra chromosome in the 21st chromosome pair of humans. Metabolomics is an alternative method in discovery of new biomarkers for the screening and diagnosis of Down syndrome. In this study, quantitative analyzes of 3-hydroxybutyric acid and 3-hydroxyisovaleric acid, selected as possible markers for prenatal diagnosis of Down syndrome were performed. LC-MS/MS analyzes were performed on a Phenomenex Luna NH2 (100 x 4.6 mm, 3 μm) column using a mobile phase mixture of 0.1% formic acid and acetonitrile containing 0.1% formic acid at a flow rate of 0.35 mL/minute. The MRM transitions were 103.0→59.0 for 3-hydroxybutyric acid and 117.1→59.0 for 3-hydroxyisovaleric acid. Under these conditions, the retention times of 3-hydroxyisovaleric acid 3-hydroxybutyric acid were 2.7 and 3.1 minute, respectively. The method was found linear from 0.1 to 10.0 μg/mL for both metabolites. The limit of detection (LOD) was 0.017 μg/mL for 3-hydroxybutyric acid and 0.003 μg/mL for 3-hydroxyisovaleric acid. The lower limit quantification (LLOQ) was 0.045 μg/mL for 3-hydroxybutyric acid and 0.008 μg/mL for 3-hydroxyisovaleric acid. The method has been proven to be selective, precise, accurate, sensitive, and robust based on the validation studies results. Finally, the method was applied to plasma samples of the pregnant women with healthy fetus (n = 30) and with Down syndrome fetus (n = 17). As a result of the analysis, a statistically significant increase (p <0.01) was observed in the 3-hydroxybutyric acid level of the group with Down syndrome compared to the healthy group. This result strengthens the use of 3-hydroxybutyric acid as an important biomarker in the prenatal screening/diagnosis of Down syndrome.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • [1] Gardiner K, Herault Y, Lott IT, Antonarakis SE, Reeves RH, Dierssen M. Down syndrome: from understanding the neurobiology to therapy. J Neurosci. 2010; 30(45): 14943-14945. [CrossRef]
  • [2] Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW, Sherman SL, Reeves RH. Down syndrome. Nat Rev Dis Primers. 2020; 6(1): 1-20. [CrossRef]
  • [3] Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishar DS, Nicolaides K. Metabolomic analysis for first-trimester Down syndrome prediction. Am J Obstet Gynecol. 2013; 208(5): 371-378. [CrossRef]
  • [4] Nemutlu E, Orgul G, Recber T, Aydin E, Ozkan E, Turgal M, Alikasifoglu M, Kır S, Beksac MS. Metabolic infrastructure of pregnant women with trisomy 21 fetuses; metabolomic analysis. Z. Geburtshilfe Neonatol. 2019; 223(05): 297-303. [CrossRef]
  • [5] Sánchez-Ribas I, Riqueros M, Vime P, Puchades-Carrasco L, Jönsson T, Pineda-Lucena A, Ballesteros A, Domínguez F, Simón C. Differential metabolic profiling of non–pure trisomy 21 human preimplantation embryos. Fertil Steril. 2012; 98(5): 1157-1164. [CrossRef]
  • [6] Engelke UF, Kremer B, Kluijtmans LA, van der Graaf M, Morava E, Loupatty FJ, Wanders RJA, Moskau D, Loss S, Bergh E, Wevers RA. NMR spectroscopic studies on the late onset form of 3‐ methylglutaconic aciduria type I and other defects in leucine metabolism. NMR Biomed. 2006; 19(2): 271-278. [CrossRef]
  • [7] Bahado-Singh RO, Akolekar R, Mandal R, Dong E, Xia J, Kruger M, Wishart D, Nicholadies K. Metabolomics and first-trimester prediction of early-onset preeclampsia. J. Matern.-Fetal Neonatal Med. 2012; 25(10): 1840-1847. [CrossRef]
  • [8] Luís PB, Ruiter JP, IJlst L, Diogo L, Garcia P, de Almeida IT, Duran M, Wanders RJ, Silva MFB. Inhibition of 3- methylcrotonyl-CoA carboxylase explains the increased excretion of 3-hydroxyisovaleric acid in valproate-treated patients. J Inherit Metab Dis. 2012; 35(3): 443-449. [CrossRef]
  • [9] Mock DM, Henrich CL, Carnell N, Mock NI. Indicators of marginal biotin deficiency and repletion in humans: validation of 3-hydroxyisovaleric acid excretion and a leucine challenge. Am J Clin Nutr. 2002; 76(5): 1061-1068. [CrossRef]
  • [10] Cevasco G, Piątek AM, Thea S. HPLC determination of D-3-hydroxybutyric acid by derivatization with a benzofurazan reagent and fluorescent detection: application in the analysis of human plasma. Clin Chim Acta. 2014; 429: 90-95. [CrossRef]
  • [11] Özkan E, Nemutlu E, Beksac MS, Kır S. GC–MS analysis of seven metabolites for the screening of pregnant women with Down syndrome fetuses. J Pharm Biomed. 2020; 188: 113427. [CrossRef]
  • [12] Miyazaki T, Honda A, Ikegami T, Iwamoto J, Monma T, Hirayama T, Saito Y, Yamashita K, Matsuzaki Y. Simultaneous quantification of salivary 3-hydroxybutyrate, 3-hydroxyisobutyrate, 3-hydroxy-3-methylbutyrate, and 2-hydroxybutyrate as possible markers of amino acid and fatty acid catabolic pathways by LC–ESI–MS/MS. Springerplus. 2015; 4(1): 1-18. [CrossRef]
  • [13] Zhang Q, Ford LA, Goodman KD, Freed TA, Hauser DM, Conner JK, Vroom KET, Toal DR. LC–MS/MS method for quantitation of seven biomarkers in human plasma for the assessment of insulin resistance and impaired glucose tolerance. J Chromatogr B. 2016; 1038: 101-108. [CrossRef]
  • [14] Reçber T, Nemutlu E, Beksaç K, Aksoy S, Kır S. Optimization and validation of a HILIC-LC-ESI-MS/MS method for the simultaneous analysis of targeted metabolites: Cross validation of untargeted metabolomic studies for early diagnosis of breast cancer. Microchem J. 2020; 159: 105559. [CrossRef]
  • [15] Horvath TD, Matthews NI, Stratton SL, Mock DM, Boysen G. Measurement of 3-hydroxyisovaleric acid in urine from marginally biotin-deficient humans by UPLC-MS/MS. A Anal. Bioanal Chem. 2011; 401(9): 2805-2810. [CrossRef]
  • [16] Perry CA, West AA, Gayle A, Lucas LK, Yan J, Jiang X, Malysheva O, Caudill MA. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet. J Nutr. 2014; 144(12): 1977-1984. [CrossRef]
  • [17] Bioanalytical Method Validation M10. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, draft version 2019.
  • [18] Bahado-Singh RO, Akolekar R, Chelliah A, Mandal R, Dong E, Kruger M, Wishart DS, Nicolaides K. Metabolomic analysis for first-trimester trisomy 18 detection. Am J Obstet Gynecol. 2013; 209(1): 65-69. [CrossRef]
APA Reçber T, ÖZKAN E, Beksac M, Kır S (2022). Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. , 136 - 144. 10.29228/jrp.110
Chicago Reçber Tuba,ÖZKAN ECE,Beksac M.Sinan,Kır Sedef Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. (2022): 136 - 144. 10.29228/jrp.110
MLA Reçber Tuba,ÖZKAN ECE,Beksac M.Sinan,Kır Sedef Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. , 2022, ss.136 - 144. 10.29228/jrp.110
AMA Reçber T,ÖZKAN E,Beksac M,Kır S Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. . 2022; 136 - 144. 10.29228/jrp.110
Vancouver Reçber T,ÖZKAN E,Beksac M,Kır S Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. . 2022; 136 - 144. 10.29228/jrp.110
IEEE Reçber T,ÖZKAN E,Beksac M,Kır S "Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS." , ss.136 - 144, 2022. 10.29228/jrp.110
ISNAD Reçber, Tuba vd. "Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS". (2022), 136-144. https://doi.org/10.29228/jrp.110
APA Reçber T, ÖZKAN E, Beksac M, Kır S (2022). Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of research in pharmacy (online), 26(1), 136 - 144. 10.29228/jrp.110
Chicago Reçber Tuba,ÖZKAN ECE,Beksac M.Sinan,Kır Sedef Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of research in pharmacy (online) 26, no.1 (2022): 136 - 144. 10.29228/jrp.110
MLA Reçber Tuba,ÖZKAN ECE,Beksac M.Sinan,Kır Sedef Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of research in pharmacy (online), vol.26, no.1, 2022, ss.136 - 144. 10.29228/jrp.110
AMA Reçber T,ÖZKAN E,Beksac M,Kır S Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of research in pharmacy (online). 2022; 26(1): 136 - 144. 10.29228/jrp.110
Vancouver Reçber T,ÖZKAN E,Beksac M,Kır S Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of research in pharmacy (online). 2022; 26(1): 136 - 144. 10.29228/jrp.110
IEEE Reçber T,ÖZKAN E,Beksac M,Kır S "Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS." Journal of research in pharmacy (online), 26, ss.136 - 144, 2022. 10.29228/jrp.110
ISNAD Reçber, Tuba vd. "Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS". Journal of research in pharmacy (online) 26/1 (2022), 136-144. https://doi.org/10.29228/jrp.110