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

Tuba Reçber; Ece Özkan; Emirhan Nemutlu; M.sinan Beksac; Sedef Kır

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

Abstract

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 3hydroxyisovaleric acid, selected as possible markers for prenatal diagnosis of Down syndrome were performed. LCMS/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 3hydroxybutyric acid as an important biomarker in the prenatal screening/diagnosis of Down syndrome.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Analytical Chemistry

Journal Section

Research Article

Authors

Tuba Reçber ^*
Türkiye

Ece Özkan This is me
Türkiye

Emirhan Nemutlu
Türkiye

M.sinan Beksac
Türkiye

Sedef Kır
Türkiye

Publication Date

June 28, 2025

Submission Date

September 4, 2021

Acceptance Date

December 3, 2021

Published in Issue

Year 2022 Volume: 26 Number: 1

IZ

https://izlik.org/JA29CH68PP

Cite

RIS / Bibtex

APA

Reçber, T., Özkan, E., Nemutlu, E., Beksac, M., & Kır, S. (2025). Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of Research in Pharmacy, 26(1), 136-144. https://izlik.org/JA29CH68PP

AMA

1.Reçber T, Özkan E, Nemutlu E, Beksac M, Kır S. Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. J. Res. Pharm. 2025;26(1):136-144. https://izlik.org/JA29CH68PP

Chicago

Reçber, Tuba, Ece Özkan, Emirhan Nemutlu, M.sinan Beksac, and Sedef Kır. 2025. “Analysis of 3-Hydroxyisovaleric Acid and 3-Hydroxybutyric Acid in Plasma Samples by LC-MS MS”. Journal of Research in Pharmacy 26 (1): 136-44. https://izlik.org/JA29CH68PP.

EndNote

Reçber T, Özkan E, Nemutlu E, Beksac M, Kır S (June 1, 2025) Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. Journal of Research in Pharmacy 26 1 136–144.

IEEE

[1]T. Reçber, E. Özkan, E. Nemutlu, M. Beksac, and S. Kır, “Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS”, J. Res. Pharm., vol. 26, no. 1, pp. 136–144, June 2025, [Online]. Available: https://izlik.org/JA29CH68PP

ISNAD

Reçber, Tuba - Özkan, Ece - Nemutlu, Emirhan - 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 26/1 (June 1, 2025): 136-144. https://izlik.org/JA29CH68PP.

JAMA

1.Reçber T, Özkan E, Nemutlu E, Beksac M, Kır S. Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. J. Res. Pharm. 2025;26:136–144.

MLA

Reçber, Tuba, et al. “Analysis of 3-Hydroxyisovaleric Acid and 3-Hydroxybutyric Acid in Plasma Samples by LC-MS MS”. Journal of Research in Pharmacy, vol. 26, no. 1, June 2025, pp. 136-44, https://izlik.org/JA29CH68PP.

Vancouver

1.Tuba Reçber, Ece Özkan, Emirhan Nemutlu, M.sinan Beksac, Sedef Kır. Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(1):136-44. Available from: https://izlik.org/JA29CH68PP