Derivatization reactions in the gas—liquid chromatographic analysis of drugs in biological fluids

Hulshoff, A.; Lingeman, H.

doi:10.1016/0731-7085(84)80040-0

Cited by 17 publications

(14 citation statements)

References 485 publications

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“…As shown in Figure 2, amine and hydroxylamine compounds can be derivatized via acylation, which is the replacement of a labile hydrogen with an acyl group [3,4]. Trifluoroacetic anhydride (TFAA) is a common acylation agent [3,5].…”

Section: Figurementioning

confidence: 99%

Formation and identification of novel derivatives of primary amine and zwitterionic drugs

2018

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Gas chromatography-mass spectrometry (GC-MS) is a "workhorse" in the analysis of controlled substances in forensic laboratories. However, many drugs are not amenable to GC-MS due to thermal instability, non-ideal interactions in the column, or both. To improve the suitability of a molecule for analysis by GC-MS, derivatization can be employed. Derivatization replaces a labile hydrogen in the analyte molecule with a more stable functional group. In this paper, three different derivatization agents were tested for effectiveness with two classes of drugs: primary amines (i.e., amphetamine and 2C-I) and zwitterions (i.e., gabapentin, lorazepam, vigabatrin, pregabalin, and clorazepate). Trifluoroacetic anhydride (TFAA) was used as an acylating agent and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was used as a silylating agent. Dimethylformamide-dimethyl acetal (DMF-DMA), which has not been previously used for derivatization of drugs, was used as an alkylating agent. DMF-DMA was found to form dimethylaminomethylene derivatives with several primary amines and zwitterions. Amphetamine, 2C-I, gabapentin, and lorazepam were all detected in their underivatized form but generally suffered from peak asymmetry and band broadening. Derivatization resulted in drastic improvements in their chromatographic behavior. Vigabatrin, clorazepate and pregabalin were not detectable in their underivatized form. However, the trimethylsilyl (TMS) derivative of clorazepate was readily detected by GC-MS, as were the TMS and trifluoroacetyl (TFA) derivatives of vigabatrin. Derivatization of pregabalin was not successful, resulting in multiple chromatographic peaks with each derivatization agent. The mass spectra of several derivatives were not found in commercially available mass spectral databases. Hence, those spectra are reported here with interpretation of their fragmentation.

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Section: Figurementioning

confidence: 99%

Formation and identification of novel derivatives of primary amine and zwitterionic drugs

2018

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“…Extensive compilations of methods and conditions can be found in references [435][436][437][438][439][440][441]. Extensive compilations of methods and conditions can be found in references [435][436][437][438][439][440][441].…”

Section: Derivatization Techniques For Gas Chromatographymentioning

confidence: 99%

“…The term "alkylation" covers a variety of techniques in which an active hydrogen atom is replaced in a chemical reaction by an alkyl or, sometimes, an aryl group [436,441,446,448,496].…”

Section: Alkylationmentioning

confidence: 99%

“…Carboxylic acids, phenols, amides and thiols are rapidly converted to the corresponding alkyl derivatives while amines are converted to the N-dimethylaminomethylene [RNH 2 -> RN=CHN(CH 3 ) 2 ] derivatives [441]. The reagents are easily hydrolyzed to dimethylformamide and the appropriate alcohol so most reactions are performed under scrupulously dry conditions.…”

Section: Variousmentioning

confidence: 99%

“…Extractive alkylation is used to derivatize acids, phenols, alcohols or amides in aqueous solution [435,441,448,502]. The pH of the aqueous phase is adjusted to ensure complete ionization of the acidic substance which is then extracted as an ion pair with a tetraalkylammonium hydroxide into a suitable immiscible organic solvent.…”

Section: Variousmentioning

confidence: 99%

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Importance of analytical methods in pharmacokinetic and drug metabolism studies

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Pharmacokinetic and drug metabolism studies first request that good analytical data are available. The various methods that permit unchanged drugs and their metabolites to be separated, identified and quantitatively assayed are briefly reviewed. The present importance of gas chromatographyhnass spectrometry is emphasized, as well as the limits of immunological assays. The sensitivity of the analytical assay has a direct impact on the validity of the pharmacokinetic model which is built up from plasma concentration data. The precision and accuracy of the assay is also critical, and it is not always easily estimated. A new significant parameter is the speed of analysis, and the resulting massive production of analytical data. New drugs coming from biotechnology, and new dosage forms, like targeted drugs, will create new analytical problems in the future. They will probably call for the development of new biological or pharmacological assay procedures, in addition to the physicochemical means of analysis.

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Derivatization reactions in the gas—liquid chromatographic analysis of drugs in biological fluids

Cited by 17 publications

References 485 publications

Formation and identification of novel derivatives of primary amine and zwitterionic drugs

Formation and identification of novel derivatives of primary amine and zwitterionic drugs

Sample Preparation for Chromatographic Analysis

Importance of analytical methods in pharmacokinetic and drug metabolism studies

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