Improved GC/MS Analysis of Opiates with Use of Oxime-TMS Derivatives

Abstract

An improved gas chromatographic/mass spectrometric (GC/MS) assay is described for the quantitation of codeine and morphine as trimethylsyl (TMS) derivatives. The TMS derivatization of ketone-containing opiates results in the formation of multiple derivatives. Some of these products have retention times close to those of codeine-TMS and morphine-TMS. When the ketoopiates are present in samples assayed for codeine and morphine in urine, they can interfere with the quantitation of these commonly targeted opiates. The assay was improved with the addition of a pre-BSTFA derivatization step, whereby hydroxylamine was used to convert the keto-opiates into the corresponding oxime derivative. These derivatives were then reacted with BSTFA to form the TMS ethers and TMS oxime derivatives. The oxime step enabled production of single derivatives for hydrocodone and hydromorphone. In addition, the retention times for the oxime-TMS derivatives were increased so that they no longer elute near the targeted drugs of codeine and morphine. The addition of the oxime step does not affect the sylation of codeine and morphine, and the accuracy and precision of this assay were unaffected.

Simultaneous analysis of Thebaine, 6-MAM and six abused opiates in postmortem fluids and tissues using Zymark® automated solid-phase extraction and gas chromatography–mass spectrometry

“…For a majority of these opiate analytes, the concentrations determined on days 4 and 7 showed no significant difference from those obtained on day 1. This agrees well with other published findings [22]. The RSD for each of the opiate compounds was less than 10% on days 4 and 7.…”

“…The LOQ for these opiaterelated compounds ranged from 0.78 to 25 ng/mL. The LOD and LOQ values determined in this experiment were superior to what had been previously reported [22].…”

“…Therefore, a trimethyl silane (TMS) derivative is most commonly used for the quantitation of opiate compounds [12,[18][19][20][21]. However, when forming TMS derivatives of ketone-containing opiates, such as hydrocodone, hydromorphone, and oxycodone, numerous derivatives for each compound can be formed due to ketoenol tautamerization [1,22]. Tautamerization can be avoided by an initial pre-derivatization reaction with hydroxylamine.…”

“…Tautamerization can be avoided by an initial pre-derivatization reaction with hydroxylamine. Hydroxylamine reacts with the ketone moiety of these opiates to form an oxime, which then forms a TMS derivative [22,23].…”

Determination of 6-oxo-morphinans, as the oximes, by difference circular dichroism spectroscopy

“…GC-MS methods have been developed for the identification of medicinal opiates and illicit drugs [21,22,23,24]. To enhance the separation, GC-MS methods often include derivatization of the keto-opiates with hydroxylamine [25,26] or methoxyamine [27,28] Fig. 1 Oxime formation by 6-oxo-morphinans Circular dichroism (CD) spectroscopy have been applied advantageously to solve different analytical problems [30,31].…”