Test Catalog

Test Id : BUAUC

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Busulfan, Intravenous Dose, Area Under the Curve, Plasma

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Guiding dosage adjustments to achieve complete bone marrow ablation while minimizing dose-dependent toxicity

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
DOSE Busulfan, IV Dose, AUC, P No Yes
BU2H Busulfan, Immediate Post Infusion No Yes
BU3H Busulfan, 1hr Post Infusion No Yes
BU4H Busulfan, 2hr Post Infusion No Yes
BU6H Busulfan, 4hr Post Infusion No Yes

Method Name
A short description of the method used to perform the test

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Busulfan, IV Dose, AUC, P

Aliases
Lists additional common names for a test, as an aid in searching

Bulsulfex

Specimen Type
Describes the specimen type validated for testing

Plasma Na Heparin

Necessary Information

The time the drug administration is started and completed, the patient's dose (mg every 6 hours), body weight (kg), and age (years) must be submitted with the specimens. Without infusion start time, exact time of specimen collection, dose, and body weight, the area under the curve and clearance cannot be calculated. Age is required for assessment of the correct dose per body weight.

 

A completed Busulfan Information: Mail-In Specimen Instructions (T559) is required.

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
DRDT2 Draw Date
DRDT3 Draw Date
DRDT4 Draw Date
DRDT6 Draw Date
DSE Initial Dose
DRTM2 Draw Time
DRTM3 Draw Time
DRTM4 Draw Time
DRTM6 Draw Time
DAT16 Infusion Start Date
TM82 Infusion Start Time
DAT17 Infusion Stop Date
TM65 Infusion Stop Time
W8 Weight

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Four plasma specimens with different collection times (keep all specimens under 1 order) are required.

 

Collection Container/Tube: Green top (sodium heparin) (Plasma gel/PST are not acceptable)

Submission Container/Tube: Plastic vials

Specimen Volume: 1 mL

Collection Instructions:

1. The first specimen should be collected immediately after completion of the first intravenous infusion of 0.8 mg/kg busulfan.

2. Additional specimens should also be collected at 1 hour, 2 hours, and 4 hours after completion of infusion.

3. Label each specimen with exact time of collection.

4. Busulfan degrades quickly at ambient temperature. Specimens must be kept in wet ice slurry or refrigerated at 4 degrees C. Specimens must be centrifuged within 2 hours after collection. Separate the plasma and transfer to individual 5-mL plastic vials, labeled with exact time of collection. Immediately freeze at -20 degrees C.

Additional Information:

This test should only be ordered when the following criteria are met:

-Busulfan dosing protocol must be intravenous administration of 0.8 mg/kg doses every 6 hours over 4 days, for a total of 16 doses

-Specimens must be collected as described below:

-1 specimen collected immediately after completion of the first 2-hour IV infusion of busulfan

-1 specimen collected 1 hour after the infusion is completed

-1 specimen collected 2 hours after the infusion is completed

-1 specimen collected 4 hours after the infusion is completed and prior to the next infusion of busulfan

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. Busulfan Information: Mail-In Specimen Instructions (T559) is required

2. If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.25 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Plasma Na Heparin Frozen (preferred) 28 days
Refrigerated 72 hours

Useful For
Suggests clinical disorders or settings where the test may be helpful

Guiding dosage adjustments to achieve complete bone marrow ablation while minimizing dose-dependent toxicity

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Busulfan is an alkylating agent used to ablate bone marrow cells prior to hematopoietic stem cell transplantation for chronic myelogenous leukemia.(1) Busulfan is typically administered intravenously (IV) at the recommended dosage of 0.8 mg/kg of actual or ideal body weight (whichever is lower) and given once every 6 hours over 4 days for a total of 16 doses. Dose-limiting toxicity of busulfan includes veno-occlusive liver disease, seizures, and coma. To avoid toxicity while ensuring busulfan dose adequacy to completely ablate the bone marrow, IV dosing should be guided by a pharmacokinetic (PK) evaluation of the area under the curve and clearance after the first dose.(2) The PK evaluation should be carried out at the end of the first dose, with results of PK testing available to facilitate dose adjustment before beginning the fifth dose.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

AREA UNDER THE CURVE

900-1500 (mcmol/L)(min)

 

CLEARANCE

2.1-3.5 (mL/minute)/kg

Interpretation
Provides information to assist in interpretation of the test results

Results of the timed collections will be used to calculate a 6-hour area under the curve (AUC). If a different dosing or specimen collection protocol is used, or if different calculations are required, contact the Laboratory Director.

 

The optimal result for AUC (6 hour) derived from this pharmacokinetic evaluation of IV busulfan is 1100 (mcmol/L)(min).

 

AUC results greater than 1500 (mcmol/L)(min) are associated with hepatic veno-occlusive disease. A dose reduction should be considered before the next busulfan infusion.

 

AUC results below 900 (mcmol/L)(min) are consistent with incomplete bone marrow ablation. A dose increase should be considered before the next busulfan infusion.

 

Clearance of busulfan in patients with normal kidney function is usually in the range of 2.1 to 3.5 (mL/min)/kg.

 

Elevated AUC is typically associated with clearance below 2.5 (mL/min)/kg, most frequently due to diminished activity of glutathione S-transferase A1-1 activity.(3)

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Failure to provide the 4 plasma specimens as described will invalidate the area under the curve calculations.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Santos GW, Tutschka PJ, Brookmeyer R, et al: Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983;309(22):1347-1353

2. Slattery JT, Sanders JE, Buckner CD, et al: Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant. 1995;16(1):31-42

3. Slattery JT, Risler LJ: Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit. 1998;20(5):543-549

4. Czerwinski M, Gibbs M, Slattery JT: Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos. 1996;24(9):1015-1019

5. Vassal G, Re M, Gouyette A: Gas chromatographic-mass spectrometric assay for busulfan in biological fluids using a deuterated internal standard. J Chromatogr. 1988;428(2):357-361

6. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 12th ed. Biomedical Publications; 2020

7. Busulfex. Package insert. Otsuka Pharmaceutical Co, Ltd; Updated January 2015. Accessed May 23, 2023. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2015/020954s014lbl.pdf

Method Description
Describes how the test is performed and provides a method-specific reference

Busulfan analysis is performed by liquid chromatography-tandem mass spectrometry with calculation of area under the curve (AUC) by integration of the time versus concentration curve from start of infusion to last specimen collection (6-hour AUC).(Unpublished Mayo method)

 

AUC and clearance are calculated after quantification of busulfan concentration in plasma samples collected at specific time points after the initial infusion.

 

The AUC is calculated by integration of the plot of time in minutes from the start of infusion until the last specimen collection (independent variable), with busulfan concentration in mcmol/L (dependent variable) and straight-line extrapolation of the immediate postinfusion busulfan concentration to time zero. Clearance is calculated as the dose divided by AUC.

 

The recommended optimal dose is calculated based on the assumption of an ideal AUC=1100 mcmol*min.(Slattery JT, Risler LJ: Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit. 1998;20(5):543-549)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Saturday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

Same day/1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

80299 x 4

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
BUAUC Busulfan, IV Dose, AUC, P 93478-6
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
DRDT2 Draw Date 33882-2
DRTM2 Draw Time 49049-0
24221 Busulfan result 93436-4
DRDT3 Draw Date 33882-2
DRTM3 Draw Time 49049-0
24222 Busulfan result 93435-6
DRDT4 Draw Date 33882-2
DRTM4 Draw Time 49049-0
24223 Busulfan result 93434-9
DRDT6 Draw Date 33882-2
DRTM6 Draw Time 49049-0
24224 Busulfan result 93433-1
DSE Initial Dose 93477-8
DAT16 Infusion Start Date 88063-3
TM82 Infusion Start Time 88060-9
DAT17 Infusion Stop Date 88062-5
TM65 Infusion Stop Time 88061-7
W8 Weight 29463-7
24220 Age 30525-0
24225 Area Under the Curve, (0-6 Hour) 93476-0
24226 Clearance 93475-2
24227 Recommended Dose 93477-8

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | PHP Pdf | CMS Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports