Synthesis of ¹³C labeled sulfur and nitrogen mustard metabolites as mass spectrometry standards for monitoring and detecting chemical warfare agents

Abstract

13C labeled (>M + 4) metabolites of nitrogen and sulfur‐based chemical warfare agent metabolites were prepared from readily available and 13C labeled commercial starting materials. The new chemical routes are efficient in the number of chemical steps, can be scaled to afford gram quantities, and occur in good yields on the basis of the 13C label. These labeled compounds are useful as internal standards in mass spectrometry for monitoring chemical warfare agents and their metabolites. Published 2012. This article is a US Government work and is in the public domain in the USA.

Synthesis of stable isotope–labeled chloroquine and amodiaquine and their metabolites

“…Therefore, diagnostic monitoring of chloroquine and amodiaquine and their metabolites by quantitative mass spectrometry has found recent increased attention. Importantly, stable isotope–labeled (SIL) reference samples have become the gold standard for facilitating accurate measurements and method development for mass spectrometry detection and quantification …”

“…We have been interested in the synthesis of SIL compounds since the 1980s; these include the syntheses of sulfur and nitrogen mustard metabolites and polyaromatics . We now report on the synthesis of SIL chloroquine and amodiaquine and their metabolic products.…”

“…Importantly, stable isotope-labeled (SIL) reference samples have become the gold standard for facilitating accurate measurements and method development for mass spectrometry detection and quantification. 9,10 We have been interested in the synthesis of SIL compounds since the 1980s; these include the syntheses of sulfur and nitrogen mustard metabolites and polyaromatics. 9,10 We now report on the synthesis of SIL chloroquine and amodiaquine and their metabolic products.…”

Synthesis of [13C6]‐labelled phenethylamine derivatives for drug quantification in biological samples

“…demonstrated the success of substituting the deuterated IS for 13 C IS in their routine analysis of amphetamine ( 1a ) and methamphetamine ( 1b ) by SIL IS synthesized in our laboratory. Moreover, the use of 13 C as label in analytes for use as IS is widely known and appreciated also in other fields of analytical chemistry …”

Synthesis of [13C4]-labeled ∆9-Tetrahydrocannabinol and 11-nor-9-Carboxy-∆9-tetrahydrocannabinol as Internal Standards for Reducing Ion Suppressing/Alteration Effects in LC/MS-MS Quantification

“…Recently, the success of substituting deuterated IS with 13 C IS has been shown in the case of amphetamine and methamphetamine quantification [16]. The use of 13 C as labeled compounds as IS is also widely known and appreciated in other fields of analytical chemistry [17,18,19,20,21]. Based on this background we disclose herein a synthesis of [ 13 C 4 ]-labeled Δ 9 -THC ( 1 ) and Δ 9 -THC-COOH ( 3 ) made via [ 13 C 4 ]-olivetol.…”