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Simultaneous quantification of levetiracetam and gabapentin in plasma by ultra-pressure liquid chromatography coupled with tandem mass spectrometry detection.
Ther Drug Monit. 2011 Apr; 33(2):209-13.TD

Abstract

INTRODUCTION

Gabapentin (Neurontin) and levetiracetam (Keppra) are anticonvulsants with novel structures and suggested therapeutic ranges of 2-10 mg/L and 6-20 mg/L, respectively. Gabapentin is also used extensively to manage neuropathic pain, and for this indication, wherein higher doses are prescribed, plasma concentrations of 15-30 mg/L are typical.

OBJECTIVE

Here, we describe a simple rapid assay to support therapeutic drug monitoring of gabapentin and levetiracetam in plasma by ultra-pressure liquid chromatography couples to tandem mass spectrometry (UPLC-MS/MS) detection.

METHODS

After the addition of internal standard and protein precipitation of patient plasma with methanol:acetonitrile in a 50:50 ratio, 1 μL of supernatant sample is injected onto an Acquity UPLC HSS T3, 1.8 μm, 2.1 × 50 mm (Waters) column. Elution occurs using a linear gradient of acetonitrile and water, each having 0.1% formic acid added. The column is eluted into a Waters Acquity UPLC TQD, operating in a positive mode to detect gabapentin at transition 172.18 > 154.11, levetiracetam at 171.11 > 126, and internal standard (3-amino-2-naphthoic acid) at 188.06 > 170. Secondary transitions for each analyte are also monitored for gabapentin at 172.18 > 137.06, levetiracetam at 171.11 > 154, and internal standard at 188.06 > 115. Runtime is 1.5 minutes per injection with baseline resolved chromatographic separation.

RESULTS

The analytical measurement ranges were 1-150 mg/L for gabapentin and for levetiracetam. Intra-assay imprecision by the coefficient of variance (CV) was less than 8% and interassay CV was less than 5% for both analytes, at 4 different concentrations. Results obtained from patient samples were compared with results generated by established high-performance liquid chromatography-UV methods with the following regression statistics: y = 1.12x - 0.77, r = 0.996, Sy, x = 0.89, and n = 29 for gabapentin and y = 0.991x + 0.70, r = 0.997, Sy, x = 2.24, and n = 30 for levetiracetam. No analytical interferences were identified.

CONCLUSION

: In summary, a simple reliable UPLC-MS/MS method was developed and validated for routine clinical monitoring of gabapentin and levetiracetam.

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Authors+Show Affiliations

Juenke JM
ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah, USA. juenkejm@aruplab.com
Brown PI
No affiliation info available
Johnson-Davis KL
No affiliation info available
McMillin GA
No affiliation info available

MeSH

AminesAnticonvulsantsChromatography, LiquidCyclohexanecarboxylic AcidsDrug MonitoringGabapentinHumansLevetiracetamPiracetamReproducibility of ResultsTandem Mass Spectrometrygamma-Aminobutyric Acid

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21297550

Citation

Juenke, JoEtta M., et al. "Simultaneous Quantification of Levetiracetam and Gabapentin in Plasma By Ultra-pressure Liquid Chromatography Coupled With Tandem Mass Spectrometry Detection." Therapeutic Drug Monitoring, vol. 33, no. 2, 2011, pp. 209-13.
Juenke JM, Brown PI, Johnson-Davis KL, et al. Simultaneous quantification of levetiracetam and gabapentin in plasma by ultra-pressure liquid chromatography coupled with tandem mass spectrometry detection. Ther Drug Monit. 2011;33(2):209-13.
Juenke, J. M., Brown, P. I., Johnson-Davis, K. L., & McMillin, G. A. (2011). Simultaneous quantification of levetiracetam and gabapentin in plasma by ultra-pressure liquid chromatography coupled with tandem mass spectrometry detection. Therapeutic Drug Monitoring, 33(2), 209-13. https://doi.org/10.1097/FTD.0b013e31820b1fce
Juenke JM, et al. Simultaneous Quantification of Levetiracetam and Gabapentin in Plasma By Ultra-pressure Liquid Chromatography Coupled With Tandem Mass Spectrometry Detection. Ther Drug Monit. 2011;33(2):209-13. PubMed PMID: 21297550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous quantification of levetiracetam and gabapentin in plasma by ultra-pressure liquid chromatography coupled with tandem mass spectrometry detection. AU - Juenke,JoEtta M, AU - Brown,Paul I, AU - Johnson-Davis,Kamisha L, AU - McMillin,Gwendolyn A, PY - 2011/2/8/entrez PY - 2011/2/8/pubmed PY - 2011/10/18/medline SP - 209 EP - 13 JF - Therapeutic drug monitoring JO - Ther Drug Monit VL - 33 IS - 2 N2 - INTRODUCTION: Gabapentin (Neurontin) and levetiracetam (Keppra) are anticonvulsants with novel structures and suggested therapeutic ranges of 2-10 mg/L and 6-20 mg/L, respectively. Gabapentin is also used extensively to manage neuropathic pain, and for this indication, wherein higher doses are prescribed, plasma concentrations of 15-30 mg/L are typical. OBJECTIVE: Here, we describe a simple rapid assay to support therapeutic drug monitoring of gabapentin and levetiracetam in plasma by ultra-pressure liquid chromatography couples to tandem mass spectrometry (UPLC-MS/MS) detection. METHODS: After the addition of internal standard and protein precipitation of patient plasma with methanol:acetonitrile in a 50:50 ratio, 1 μL of supernatant sample is injected onto an Acquity UPLC HSS T3, 1.8 μm, 2.1 × 50 mm (Waters) column. Elution occurs using a linear gradient of acetonitrile and water, each having 0.1% formic acid added. The column is eluted into a Waters Acquity UPLC TQD, operating in a positive mode to detect gabapentin at transition 172.18 > 154.11, levetiracetam at 171.11 > 126, and internal standard (3-amino-2-naphthoic acid) at 188.06 > 170. Secondary transitions for each analyte are also monitored for gabapentin at 172.18 > 137.06, levetiracetam at 171.11 > 154, and internal standard at 188.06 > 115. Runtime is 1.5 minutes per injection with baseline resolved chromatographic separation. RESULTS: The analytical measurement ranges were 1-150 mg/L for gabapentin and for levetiracetam. Intra-assay imprecision by the coefficient of variance (CV) was less than 8% and interassay CV was less than 5% for both analytes, at 4 different concentrations. Results obtained from patient samples were compared with results generated by established high-performance liquid chromatography-UV methods with the following regression statistics: y = 1.12x - 0.77, r = 0.996, Sy, x = 0.89, and n = 29 for gabapentin and y = 0.991x + 0.70, r = 0.997, Sy, x = 2.24, and n = 30 for levetiracetam. No analytical interferences were identified. CONCLUSION: : In summary, a simple reliable UPLC-MS/MS method was developed and validated for routine clinical monitoring of gabapentin and levetiracetam. SN - 1536-3694 UR - https://www.unboundmedicine.com/medline/citation/21297550/Simultaneous_quantification_of_levetiracetam_and_gabapentin_in_plasma_by_ultra_pressure_liquid_chromatography_coupled_with_tandem_mass_spectrometry_detection_ L2 - https://doi.org/10.1097/FTD.0b013e31820b1fce DB - PRIME DP - Unbound Medicine ER -