HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in Mouse Brain Using Clean Screen FASt™ Column Extraction

Justin L Poklis, Deborah J Clay, Bogna M Ignatowska-Jankowska, Chiara Zanato, Ruth A Ross, Iain R Greig, Rehab A Abdullah, Mohammed A Mustafa, Aron H Lichtman, Alphonse Poklis

Research output: Contribution to journalArticle

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Abstract

A high-performance liquid chromatography tandem mass spectrometry method was developed for the detection and quantification of 6-methyl-3-(2-nitro-1-(thiophen-2-yl)propyl)-2-phenyl-1H-indole (ZCZ-011) using 2-phenylindole as the internal standard (ISTD). ZCZ-011 was synthesized as a possible positive allosteric modulator with the CB1 cannabinoid receptor. The analytical method employs a rapid extraction technique using Clean Screen FASt™ columns with a Positive Pressure Manifold. FASt™ columns were originally developed for urine drug analysis but we have successfully adapted them to the extraction of brain tissue. Chromatographic separation was performed on a Restek Allure Biphenyl 5 µ, 100 × 3.2 mm column (Bellefonte, PA). The mobile phase consisted of 1:9 deionized water with 10 mmol ammonium acetate and 0.1% formic acid-methanol. The following transition ions (m/z) were monitored for ZCZ-011: 363 > 207 and 363 > 110 and for the ISTD: 194 > 165 and 194 > 89. The FASt™ columns lowered and stabilized the ion suppression over the linear range of the assay (40-4,000 ng/g). The method was evaluated for recovery, ion suppression, accuracy/bias, intraday and interday precision, bench-top stability, freeze-thaw and post-preparative stability. The method was successfully applied to brain tissue from C57BL/6J mice that received intraperitoneal (i.p.) injections with 40 mg/kg of ZCZ-011 or vehicle.

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalJournal of analytical toxicology
Volume39
Issue number5
Early online date3 Mar 2015
DOIs
Publication statusPublished - 1 Jun 2015

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Cannabinoid Receptors
brain
Brain
High Pressure Liquid Chromatography
Pharmacology
Ions
formic acid
Tissue
ion
Deionized water
Formic acid
High performance liquid chromatography
Modulators
Mass spectrometry
Assays
Methanol
Cannabinoid Receptor CB1
urine
methanol
liquid chromatography

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HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in Mouse Brain Using Clean Screen FASt™ Column Extraction. / Poklis, Justin L; Clay, Deborah J; Ignatowska-Jankowska, Bogna M; Zanato, Chiara; Ross, Ruth A; Greig, Iain R; Abdullah, Rehab A; Mustafa, Mohammed A; Lichtman, Aron H; Poklis, Alphonse.

In: Journal of analytical toxicology, Vol. 39, No. 5, 01.06.2015, p. 353-359.

Research output: Contribution to journalArticle

Poklis, Justin L ; Clay, Deborah J ; Ignatowska-Jankowska, Bogna M ; Zanato, Chiara ; Ross, Ruth A ; Greig, Iain R ; Abdullah, Rehab A ; Mustafa, Mohammed A ; Lichtman, Aron H ; Poklis, Alphonse. / HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in Mouse Brain Using Clean Screen FASt™ Column Extraction. In: Journal of analytical toxicology. 2015 ; Vol. 39, No. 5. pp. 353-359.
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abstract = "A high-performance liquid chromatography tandem mass spectrometry method was developed for the detection and quantification of 6-methyl-3-(2-nitro-1-(thiophen-2-yl)propyl)-2-phenyl-1H-indole (ZCZ-011) using 2-phenylindole as the internal standard (ISTD). ZCZ-011 was synthesized as a possible positive allosteric modulator with the CB1 cannabinoid receptor. The analytical method employs a rapid extraction technique using Clean Screen FASt™ columns with a Positive Pressure Manifold. FASt™ columns were originally developed for urine drug analysis but we have successfully adapted them to the extraction of brain tissue. Chromatographic separation was performed on a Restek Allure Biphenyl 5 µ, 100 × 3.2 mm column (Bellefonte, PA). The mobile phase consisted of 1:9 deionized water with 10 mmol ammonium acetate and 0.1{\%} formic acid-methanol. The following transition ions (m/z) were monitored for ZCZ-011: 363 > 207 and 363 > 110 and for the ISTD: 194 > 165 and 194 > 89. The FASt™ columns lowered and stabilized the ion suppression over the linear range of the assay (40-4,000 ng/g). The method was evaluated for recovery, ion suppression, accuracy/bias, intraday and interday precision, bench-top stability, freeze-thaw and post-preparative stability. The method was successfully applied to brain tissue from C57BL/6J mice that received intraperitoneal (i.p.) injections with 40 mg/kg of ZCZ-011 or vehicle.",
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AU - Poklis, Justin L

AU - Clay, Deborah J

AU - Ignatowska-Jankowska, Bogna M

AU - Zanato, Chiara

AU - Ross, Ruth A

AU - Greig, Iain R

AU - Abdullah, Rehab A

AU - Mustafa, Mohammed A

AU - Lichtman, Aron H

AU - Poklis, Alphonse

N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - A high-performance liquid chromatography tandem mass spectrometry method was developed for the detection and quantification of 6-methyl-3-(2-nitro-1-(thiophen-2-yl)propyl)-2-phenyl-1H-indole (ZCZ-011) using 2-phenylindole as the internal standard (ISTD). ZCZ-011 was synthesized as a possible positive allosteric modulator with the CB1 cannabinoid receptor. The analytical method employs a rapid extraction technique using Clean Screen FASt™ columns with a Positive Pressure Manifold. FASt™ columns were originally developed for urine drug analysis but we have successfully adapted them to the extraction of brain tissue. Chromatographic separation was performed on a Restek Allure Biphenyl 5 µ, 100 × 3.2 mm column (Bellefonte, PA). The mobile phase consisted of 1:9 deionized water with 10 mmol ammonium acetate and 0.1% formic acid-methanol. The following transition ions (m/z) were monitored for ZCZ-011: 363 > 207 and 363 > 110 and for the ISTD: 194 > 165 and 194 > 89. The FASt™ columns lowered and stabilized the ion suppression over the linear range of the assay (40-4,000 ng/g). The method was evaluated for recovery, ion suppression, accuracy/bias, intraday and interday precision, bench-top stability, freeze-thaw and post-preparative stability. The method was successfully applied to brain tissue from C57BL/6J mice that received intraperitoneal (i.p.) injections with 40 mg/kg of ZCZ-011 or vehicle.

AB - A high-performance liquid chromatography tandem mass spectrometry method was developed for the detection and quantification of 6-methyl-3-(2-nitro-1-(thiophen-2-yl)propyl)-2-phenyl-1H-indole (ZCZ-011) using 2-phenylindole as the internal standard (ISTD). ZCZ-011 was synthesized as a possible positive allosteric modulator with the CB1 cannabinoid receptor. The analytical method employs a rapid extraction technique using Clean Screen FASt™ columns with a Positive Pressure Manifold. FASt™ columns were originally developed for urine drug analysis but we have successfully adapted them to the extraction of brain tissue. Chromatographic separation was performed on a Restek Allure Biphenyl 5 µ, 100 × 3.2 mm column (Bellefonte, PA). The mobile phase consisted of 1:9 deionized water with 10 mmol ammonium acetate and 0.1% formic acid-methanol. The following transition ions (m/z) were monitored for ZCZ-011: 363 > 207 and 363 > 110 and for the ISTD: 194 > 165 and 194 > 89. The FASt™ columns lowered and stabilized the ion suppression over the linear range of the assay (40-4,000 ng/g). The method was evaluated for recovery, ion suppression, accuracy/bias, intraday and interday precision, bench-top stability, freeze-thaw and post-preparative stability. The method was successfully applied to brain tissue from C57BL/6J mice that received intraperitoneal (i.p.) injections with 40 mg/kg of ZCZ-011 or vehicle.

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