Frozen Aliquotting Preserves Biomolecule Integrity

Frozen Aliquotting in Drug DevelopmentFrozen aliquotting prevents degradation due to freeze-thaw, improving ADME, Tox and

clinical PK results for labile pro-drugs, peptides, and antibody-drug conjugates. Frozen

aliquotting enables quantitative analysis of blood samples. Using frozen aliquotting for

whole blood, which cannot be assayed reliably when thawed, eliminates processing

steps and improves the accuracy of drug and biomarker test results.

Frozen sample aliquots are easily distributed in all phases of clinical trials,

facilitating multi-site testing and enabling pre-analytical sample QC and expansion of

testing parameters. Uncompromised parent samples can be maintained for reference

or retrospective studies.

You can with Frozen Aliquotting.

“We’re performing DMPK and ADME/Tox testing. Can we eliminate freeze-thaw cycles to analyze unstable compounds?”

“My trial requires clinical chemistry and biomarker testing. Can I distribute aliquots to multiple labs without thawing?”

“We’re having trouble with incurred sample reanalysis. Can we avoid freeze-thaw cycles to improve ISR results?”

Bioanalysis

STORE PARENT SAMPLE

Archive for ISR or retrospective testing

TEST ALIQUOTS

Use frozen aliquots to complete multiple tests

CORE SAMPLE

Generate Frozen Aliquots

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Seeing is BelievingSchedule an on-site demonstration of the CXT 353 Frozen Sample Aliquotter or a demonstration of the CXT 750 Automated Frozen Sample Aliquotter.

Top Five Benefits of Frozen Aliquotting

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Basque Engineering and Science, 33 Centre Street, Danvers, MA 01923 | 1.617.962.0309 | www.basque-engsci.com cryo-bioanalysis/9-2017

Test Labile Compounds5% to 10% of drug molecules are inherently unstable. Frozen aliquotting of

tissue and biofluids stabilizes small molecules and peptides for ADME/Tox

and DMPK testing. Frozen aliquots can be directly deposited into organic

solvent for LC/MS-MS analysis. In the study below completed at GSK, two

small molecules started degrading following 1 to 2 freeze-thaw cycles, but

maintained integrity with frozen aliquotting.

Cisatracurium in Human Plasma

0 1 2 3 4

Peak

Are

a C

ount

s

Time Point

100000

80000

60000

40000

20000

0

Cisatracurium in Rat Plasma

0 1 2 3 4

Peak

Are

a C

ount

s

Time Point

100000

80000

60000

40000

20000

0

Caffeic Acid in Human Plasma

0 1 2 3 4

Peak

Are

a C

ount

s

Time Point

5000

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3000

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1000

0

Caffeic Acid in Rat Plasma

0 1 2 3 4

Peak

Are

a C

ount

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Time Point

5000

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0

FIGURE 1. CAFFEIC ACID AND CISATRACURIUM WERE SPIKED INTO HUMAN AND RAT PLASMA. RECOVERY

VIA LC-MS/MS WAS TESTED IN THE FRESH SOLUTION AND FOLLOWING FREEZE-THAW. THE GRAPHS SHOW

PEAK AREA COUNTS FOLLOWING 0 TO 4 FREEZE-THAW CYCLES.

Analyze Drug Distribution in TissueA critical aspect of drug development is an understanding of tissue

distribution and metabolism.

Comparing levels in heart, lung, liver,

kidney, and brain provides important

information regarding drug function

and clearance1.

Analyzing distribution within a specific

tissue type can help researchers

determine how certain drugs penetrate

the heart or understand the distribution of brain penetrative compounds.2,3

Frozen aliquotting enables researchers to collect precise frozen tissue

sections and compare distinct locations within a sample.

1. Tan, et al. (2014). J. Pharmaceutical Tech. & Drug Rsch., doi: 10.7243/2050-120X-3-1

2. Tylutki, Z., et al. (2015). Biopharm. Drug Dispos., 36(6):337-351

3. Swales, J.G. et al. (2015). Anal. Chem., 87(19):10146-52

ANALYZE LABILE DRUG COMPOUNDS

Access samples without thawing

SHIP SAMPLES TO MULTIPLE LABS

Distribute frozen aliquots

IMPROVE ISR RESULTS

Avoid freeze-thaw cycles

ENABLE PRE- ANALYTICAL QC

Test frozen aliquots for sample quality

STUDY DRUG DISTRIBUTION

Capture precise tissue sections

Freeze-Thaw Aliquotting Frozen Aliquotting Baseline Extrapolated

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