Stability studies of vorinostat and its two metabolites in human plasma, serum and urine.
Author(s): Du L, Musson DG, Wang AQ
Publication: J Pharm Biomed Anal, 2006, Vol. 42, Page 556-64
PubMed ID: 16824724 PubMed Review Paper? No
Suggested by: ISBER
Purpose of Paper
The purpose of this paper was to evaluate the stability of vorinostat, vorinostat O-glucuronide (M1) and 4-anilino-4-oxobutanoic acid (M2) in plasma, serum and urine specimens.
Conclusion of Paper
Storage of heparinized plasma at -70 degrees C for up to 5 weeks, serum for up to 57 weeks, or urine specimens for up to 58 weeks did not affect vorinostat or its metabolites. In neutral or acidified EDTA plasma, vorinostat declined by about 10% during the first week of storage at -70 degrees C but then stabilized. M1 was found to be more stable with storage in neutral plasma than acidified plasma, and M2 was relatively stable in both. Up to 3 freeze-thaw cycles had no effect on vorinostat, M1 or M2 levels in EDTA plasma, serum, or urine specimens. However, in heparinized plasma specimens, 3 freeze-thaw cycles led to an approximately 10% reduction in vorinostat levels. Storage of blood specimens for up to 180 minutes prior to centrifugation did not result in significant changes in serum concentrations of vorinostat, M1 or M2.
Studies
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Study Purpose
The purpose of this study was to determine the effects of storage and freeze-thaw cycling on vorinostat, M1 and M2 in neutral and acidified EDTA plasma, heparin plasma, serum and urine specimens. For all specimens vorinostat, M1 and M2 were added to the specimen prior to storage.
Summary of Findings:
Storage of heparinized plasma at -70 degrees C for up to 5 weeks, serum for up to 57 weeks, or urine specimens for up to 58 weeks did not affect vorinostat or its metabolites. In neutral or acidified EDTA plasma, vorinostat declined by about 10% during the first week of storage at -70 degrees C but then stabilized. M1 was found to be more stable with storage in neutral plasma than acidified plasma, and M2 was relatively stable in both. Acidification of plasma specimens with formic acid led to decreased precision of the M1 and M2 assays, and acidification with high concentrations of acetic acid led to reduced precision and accuracy of M1 and M2 at low concentrations. Up to 3 freeze-thaw cycles had no effect on vorinostat, M1 or M2 levels in EDTA plasma, serum, or urine specimens. However, in heparinized plasma specimens, 3 freeze-thaw cycles led to an approximately 10% reduction in vorinostat levels. Little conversion between vorinostat, M1 and M2 in EDTA plasma specimens was observed. Storage of blood specimens for up to 180 minutes at room temperature prior to centrifugation did not result in significant changes in serum concentrations of vorinostat, M1 or M2.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Not specified
Platform:
Analyte Technology Platform Small molecule LC-MS or LC-MS/MS Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Biospecimen location Plasma
Serum
Urine
Biospecimen Acquisition Anticoagulant EDTA
Heparin
Storage Time at room temperature 15 min
30 min
60 min
120 min
180 min
Storage Storage duration 0 weeks
1 week
2 weeks
5 weeks
7 weeks
9 weeks
10 weeks
57 weeks
58 weeks
Storage Freeze/thaw cycling 0 cycles
3 cycles
Storage Storage temperature -70 degrees C
Biospecimen Aliquots and Components pH 4.7
7