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Clin Biochem. 2016 Sep;49(13-14):1092-5. doi: 10.1016/j.clinbiochem.2016.04.007. Epub 2016 Apr 27.

Development of a liquid chromatography-tandem mass spectrometry method to address the increased utilization of umbilical cord in the assessment of in utero drug exposure.

Author information

1
ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA.
2
ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah Health Sciences Center, Department of Pathology, 15 North Medical Drive East, Ste #1100, Salt Lake City, UT 84112, USA.
3
ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah Health Sciences Center, Department of Pathology, 15 North Medical Drive East, Ste #1100, Salt Lake City, UT 84112, USA. Electronic address: frederick.g.strathmann@aruplab.com.

Abstract

OBJECTIVES:

The method described supports the detection of drugs and drug metabolites in the assessment of in utero drug exposure. The presented method employs liquid chromatography-tandem mass spectrometry (LC-MS/MS) as an alternative to a previously validated method using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS). A reduction in required chromatographic time and consolidation from two injections to one injection per sample was desired to reduce turnaround time while maintaining the high specificity required.

DESIGN AND METHODS:

Homogenized and extracted umbilical cord samples were analyzed using LC-TOF/MS and LC-MS/MS. The LC-MS/MS chromatographic method used a 3.5min gradient with an injection-to-injection time of 5min. Dynamic multiple reaction monitoring was utilized.

RESULTS:

A 55% reduction in total analytical time was achieved by incorporating positive and negative mode acquisition in a single injection with the LC-MS/MS (5min cycle time) compared to the LC-TOF/MS method that required two total injections (one for positive mode, one for negative mode) and a combined ~11.5min cycle time. 514 patient samples were analyzed by both methods over 20 days. Of the 260 LC-TOF/MS negative samples, 259 were LC-MS/MS negative. Inter-assay imprecision conducted over 20days using the 50% and 150% QC samples yielded $_amp_$gt;97% qualitative acceptance and an average percent deviation from the target of 12% and 21%, respectively, using a single point calibration strategy.

CONCLUSIONS:

In comparison to the existing LC-TOF/MS method, the LC-MS/MS method delivered the required specificity in a single injection with a 55% reduction in instrument time. Use of a single-point calibration standard and eight representative internal standards provided adequate accuracy for the quantitative assessment of quality control results with qualitative reporting of patient results.

KEYWORDS:

Drugs of abuse; In utero drug detection; Tandem mass spectrometry; Time-of-flight mass spectrometry; Umbilical cord tissue

[Indexed for MEDLINE]

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