Trimethylsilyl Reagents Research Articles

Beyond hydrophobisation: Deciphering the surprising reactivity of trimethylsilyl reagents towards graphene oxide

Trimethylsilylation of metal oxide surfaces (silica, titania…) is a common way to empower the handled supports with outstanding stability. This hydrophobisation prevailed in vital domains including chromatographic column, adsorption-based membranes and heterogeneous catalysis, where hydrolytic stability constituted a challenging issue. In spite of its benefits, trimethylsilylation of graphene oxide has been only sporadically investigated and this underlooked chemistry needs to be accurately addressed for further tailoring the surface properties of graphene materials. With this aim, we herein screened a set of commercially available trimethylsilyl reagents for end-cuping the surface of graphene oxide. Surprisingly, meticulous investigations show that these reagents behave primarily as nucleophiles and induce oxirane opening, with a diverging pattern depending on the functional group linked to trimethylsilyl fragments. Specifically: i) trimethylsilylchloride and trimethylsilyltriflate are not suitable because of the substantial side products formed under acidic conditions; ii) trimethylsilylimidazolium reacts rather through its imidazolium group with the simultaneous elimination of trimethylsilyl groups; iii) bis-silylated reagents like hexamethyldisilazane and N,O-bis-trimethylsilyl-trifluoroacetamide enable anchoring at least one functional arm while liberating the second trimethylsilyl moity. The introduced functionalities enhance the dispersion of the newly prepared graphenes in liquid medium, thereby broadening the library of solvents suitable for their handling and offering more possibilities for the ink processability. Regardless of the starting reagent, the resulting functionalisation do not compromise the anchoring ability of the graphene surface as illustrated by supporting InP/ZnS semiconductor nanocrystals. In the whole, these serendipitous findings challenge the conventional wisdom about the reactivity of trimethylsilyl reagents that was primarly associated to surface hydrophobisation, opening indeed new possibilities for graphene functionalisation and further use in materials science.

Chemical transformation of cannabidiol into psychotropic cannabinoids under acidic reaction conditions: Identification of transformed products by GC-MS.

Recently, cannabidiol (CBD), one of the major components of the Cannabis species, has been a focus in the cannabis industry due to its various pharmacological effects. Interestingly, CBD can be converted into several psychoactive cannabinoids, such as 9-tetrahydrocannabinol (Δ9-THC) and its structural isomers, under acidic reaction conditions. In this study, chemical transformation of CBD in ethanol solution was conducted with variation in pH at 2.0, 3.5, and 5.0 by addition of 0.1 M hydrochloric acid (HCl). These resulting solutions were derivatized with trimethylsilyl (TMS) reagent and analyzed using GC/MS-scan mode. Time profiles of CBD degradation and transformation of products were examined according to variations in pH and temperature. Several transformed products produced after the acidic reaction of CBD were identified by matching retention times and mass spectra to authentic standards. Regarding the identification of products without authentic standards, the EI-mass spectra of such cannabinoid-OTMS derivatives were interpreted according to structural class, suggesting mass fragmentation pathways. From the GC/MS data, Δ9-THC, CBC, and ethoxy-hexahydrocannabinol (HHC) analogs were shown to be major components, and THC isomers (Δ8- and Δ10-THCs) and 9-hydroxy-HHC were observed as minor components. Using time profile data, the acidity of the reaction solution was an important factor in degradation of CBD. Degradation of CBD and formation of THC rarely occurred at pH 5.0, even at 70 °C with a long process time of 24 h. In contrast, degradation of CBD occurred readily at pH 3.5 and 30 °C over a short process time and was further accelerated by lowering pH, increasing temperature, and lengthening the process time. Based on profile data and identified transformed products, formation pathways from the degradation of CBD under acidic reaction conditions are suggested. Among the transformed products, seven components are known to have psychoactive effects. Thus, industrial CBD manufacturing processes in food and cosmetic products should be carefully controlled. These results will provide important guidelines on the control of manufacturing processes, storage, fermentation processes, and new regulation in industrial applications of CBD.

Synthesis, Reactivity, and Bonding of Gold(I) Fluorido-Phosphine Complexes.

Gold(I) fluorido complexes with phosphine ligands have been synthesized from their respective iodido precursors. The bonding situation in comparison between complexes bearing phosphines and N-heterocyclic carbenes (NHCs) was explored quantum-chemically, obtaining similar results for both. Calculations of the 19F NMR chemical shifts match the experimental values well, including the approximately 40 ppm low-field shifts for the phosphine complexes compared to the NHC complexes, in spite of similar negative charges on fluorine. The reactivity of the highly water-sensitive gold(I) fluorido complexes was studied, resulting in substitution at the metal using trimethylsilyl reagents. The compounds studied were characterized using NMR as well as X-ray diffraction methods.

Tuning the interfacial stoichiometry of InP core and InP/ZnSe core/shell quantum dots

We demonstrate fine-tuning of the atomic composition of InP/ZnSe quantum dots (QDs) at the core/shell interface. Specifically, we control the stoichiometry of both anions (P, As, S, and Se) and cations (In and Zn) at the InP/ZnSe core/shell interface and correlate these changes with the resultant steady-state and time-resolved optical properties of the nanocrystals. The use of reactive trimethylsilyl reagents results in surface-limited reactions that shift the nanocrystal stoichiometry to anion-rich and improve epitaxial growth of the shell layer. In general, anion deposition on the InP QD surface results in a redshift in the absorption, quenching of the excitonic photoluminescence, and a relative increase in the intensity of broad trap-based photoluminescence, consistent with delocalization of the exciton wavefunction and relaxation of exciton confinement. Time-resolved photoluminescence data for the resulting InP/ZnSe QDs show an overall small change in the decay dynamics on the ns timescale, suggesting that the relatively low photoluminescence quantum yields may be attributed to the creation of new thermally activated charge trap states and likely a dark population that is inseparable from the emissive QDs. Cluster-model density functional theory calculations show that the presence of core/shell interface anions gives rise to electronic defects contributing to the redshift in the absorption. These results highlight a general strategy to atomistically tune the interfacial stoichiometry of InP QDs using surface-limited reaction chemistry allowing for precise correlations with the electronic structure and photophysical properties.

Graphene Oxide-Ionic Liquid Used As Solid-Phase Microextraction Coating For Polyphenolic Compounds' Extraction And Determination With GC-MS After On-Fiber Derivatization In Wine

We describe the use of a home-made fiber coated by graphene oxide modified by an ionic liquid having methylimidazolium cation with an amino-functional group for the extraction of polyphenolic compounds (P.C.s). We then performed the determination by gas chromatography coupled with mass spectrometry after on-fiber derivatization. The authors optimized the main parameters influencing the extraction and derivatization processes. The on-fiber derivatization was employed within 15 min at 60 ºC using 20 µL of trimethylsilyl reagents. Under the optimized conditions, the calibration curves for 12 P.C.s were linear from 0.1 to 1000 µg/L, and the detection limits were between 0.02 and 0.1 µg/L. We determined the single fiber repeatability obtained for all calibration points and the fiber to fiber reproducibility for 100 µg/L to be < 14.82% and < 5.87%, respectively. The extraction efficacy of the home-made fiber due to high intermolecular and electrostatic attractions was much better than the commercial fibers. We successfully applied the method to the analysis of P.C.s in wine samples with the recoveries from 72.8 to 99.9%.

Quantification of Arbutin in Plant Extracts by Stable Isotope Dilution Gas Chromatography–Mass Spectrometry

Arbutin is a skin-whitening agent found in plants such as the Ericaceae species. Herein, we report the development and validation of a method based on gas chromatography–mass spectrometry for the analysis of arbutin in plant extracts. Prior to analysis, silylation with trimethylsilyl (TMS) reagent produced 5TMS and 4TMS derivatives, for which the peak area ratios varied significantly prior to sample injection. However, the use of [d4]-arbutin as an internal standard overcame this issue, with little variation in the observed peak area ratios. Method validation confirmed the excellent linearity (r2 = 0.9989), recovery (accuracy 101.4–105.7%), precision (relative standard deviation ≤ 3.43%), limit of detection (0.03 μg mL−1), and limit of quantitation (0.08 μg mL−1) of this novel method. Finally, our method was applied to the detection of arbutin in various plant species. To the best of our knowledge, arbutin was detected and measured in Prismatomeris tetrandra and Phyllanthus reticulatus samples for the first time.

Chalcogenide and pnictide nanocrystals from the silylative deoxygenation of metal oxides

Transition metal chalcogenides and pnictides are interesting in optoelectronics and catalysis. We present a generalized method to transform preformed metal oxide nanocrystals into sulfides, selenides, or phosphides via silylative deoxygenation with trimethylsilyl reagents. In all reactions studied, simultaneous decomposition of excess silyl reagent produces a protective, amorphous silica coating around the newly formed nanocrystals.

Tp*Cu(I)-CN-SiL2-NC-Cu(I)Tp*--a hexacoordinate Si-complex as connector for redox active metals via π-conjugated ligands.

Hexacoordinate silicon complexes L2SiX2 (L = a 2-benzoylpyrrol-1-yl derivative, X = CN, NCS) were synthesized from L2SiCl2 by ligand exchange with trimethylsilyl reagents Me3SiX. In the presence of [Tp*CuNCMe] and Me3SiCN the silicon complex L2Si(NC(CuTp*))2 was obtained, which contains a linear Cu-CN-Si-NC-Cu unit (Tp* = hydrotris(3,5-dimethylpyrazolyl)borato).

Determination of allergenic hydroperoxides in essential oils using gas chromatography with electron ionization mass spectrometry

Fragrance monoterpenes are widely used commercially due to their pleasant scent. In previous studies, we have shown that air-exposed monoterpenes form hydroperoxides that are strong skin sensitizers. Methods for detection and quantification of the hydroperoxides in essential oils and scented products are thus desirable. Due to thermolability and low UV absorbance, this is a complicated task. We have recently developed a sensitive LC-ESI-MS method, but with limited structural information and separation efficiency for positional isomers and stereoisomers. In the present study, we investigated derivatization with a trimethyl silyl reagent and subsequent GC with electron ionization MS for the determination of monoterpene hydroperoxides. All investigated monoterpene hydroperoxides could be chromatographed as thermostable trimethyl silyl derivatives and yielded the fragment m/z 89 ([OSi(CH3)3](+)) at a higher extent compared to corresponding alcohols. Limonene-2-hydroperoxide and four other hydroperoxide isomers of limonene were separated and detected in sweet orange oil autoxidized for two months. The concentration of limonene-2-hydroperoxide isomers was found to be 19 μg/mg in total. Also isomers of linalyl acetate hydroperoxide and linalool hydroperoxide were detected in autoxidized petitgrain oil (two months). The presented GC-MS method showed concentrations in the same order as previous LC-MS/MS analysis of the same type of oils.

P-Tolyl isocyanate derivatization for analysis of CWC-related polar degradation products by mass spectrometry

Most of the precursors and/or degradation products related to the Chemical Weapons Convention (CWC) are polar. Identification of these molecules in environmental samples provides clues regarding the alleged usage and/or synthesis of the parent toxic chemicals. Such polar compounds need to be derivatized in order to analyze them by gas chromatography-mass spectrometry (GC-MS). In this study, we developed a new derivatizing reagent, para-tolyl isocyanate (PTI), for derivatization of polar CWC-related compounds. The PTI reagent selectively derivatizes the -OH and/or-SH functional groups with high efficiency, but does not react with carboxylic acid (-COOH) or phosphonic acid (-(O)P(OH)2) groups. The PTI derivatives of dialkyl aminoethanols, dialkyl aminoethanol-N-oxides, and 3-quinuclidinol were successfully eluted through GC, and their electron ionization (EI) mass spectra were distinct and provided the structure information by which the isomeric compounds can be easily distinguished. We also calculated the GC-retention index values that can be used for further confirmation of the target compounds. All the studied PTI derivatives can be analyzed by EI-MS with direct insertion probe and/or by direct electrospray ionization mass spectrometry (ESI-MS) together with the MS-MS data; both sets of data provide full structure information. The PTI reagent was found to be better in some respects than the conventional bistrimethylsilyl trifluoroacetamide (BSTFA), a trimethyl silylating reagent. The PTI reagent is commercially available, and the PTI derivatives are highly stable for months and are not sensitive to moisture. The applicability of the PTI derivatization for trace-level determination of the target CWC-related polar compounds in environmental matrices and in human plasma samples is also evaluated.

Optimization of matrix solid-phase dispersion for the rapid determination of salicylate and benzophenone-type UV absorbing substances in marketed fish

A simple and effective method for the rapid determination of five salicylate and benzophenone-type UV absorbing substances in marketed fish is described. The method involves the use of matrix solid-phase dispersion (MSPD) prior to their determination by on-line silylation gas chromatography tandem mass spectrometry (GC–MS/MS). The parameters that affect the extraction efficiency were optimized using a Box–Behnken design method. The optimal extraction conditions involved dispersing 0.5g of freeze-dried powdered fish with 1.0g of Florisil using a mortar and pestle. This blend was then transferred to a solid-phase extraction (SPE) cartridge containing 1.0g of octadecyl bonded silica (C18), as the clean-up co-sorbent. The target analytes were then eluted with 7mL of acetonitrile. The extract was derivatized on-line in the GC injection-port by reaction with a trimethylsilylating (TMS) reagent. The TMS-derivatives were then identified and quantitated by GC–MS/MS. The limits of quantitation (LOQs) were less than 0.1ng/g.

Titanium(IV) Trifluoromethyl Complexes: New Perspectives on Bonding from Organometallic Fluorocarbon Chemistry

Trifluoromethyltrimethylsilane, (CH3)3SiCF3, in the presence of CsF serves as an excellent CF3 group-transfer reagent, and reaction with Cp2TiF2 in THF gives the titanocene trifluoromethyl fluoride complex Cp2Ti(CF3)(F) (1; Cp = C5H5) in 60% isolated yield. Reaction of complex 1 with the trimethylsilyl reagents, (CH3)3SiX (X = OTf = OSO2CF3, Cl, Br, I, N3, and OSO2Ph), in a tetrahydrofuran or toluene solution affords the corresponding Ti–CF3 derivatives Cp2Ti(CF3)(X) (X = OTf (2), Cl (12), Br (13), I (14), N3 (15), and OSO2Ph (16)) in good isolated yields of 67–84%. These compounds have been characterized by a combination of reactivity studies, IR and 1H/13C{1H}/19F NMR spectroscopies, and single-crystal X-ray diffraction. The Ti–CF3 linkage in these complexes is remarkably robust, and although the α-C–F bonds are elongated, there is no evidence of an α-fluoride (Ti···F–CF2) between the electrophilic Ti(IV) metal center and any of the C–F bonds in the trifluoromethyl group in the solid-state or in solution. In the solid-state, these complexes are shock-sensitive; energetic decomposition of Cp2Ti(CF3)(F) (1) produces uniform spherical nanoparticles ranging from ∼70 to 120 nm in size and porous fluorinated oligomers and polymers containing both −(CF2–CF2)– and −(CF2–CFH)– units, as determined by a combination of SEM, XRD, XRF, XPS, and 19F MAS NMR. Density functional theory results show good agreement with experimental structural data obtained for Cp2Ti(CF3)(X) (X = F (1), OTf (2), Cl (12), N3 (15)) and accurately predicts longer Ti–CF3 distances than for each specific CH3 analogue, and the trend extends to structurally related Zr and Hf analogues. Simpler model compounds from groups 4 and 8 (M(CH3)4, M(CH3)3(CF3), M(CH3)3(CCl3), and M(CH3)3(CF2CF2CF2CF3); M = Ti, Zr, Hf, Fe, Ru, Os)) were also examined and show that, for group 4 complexes, π-bonding is a significant factor in shortening the strongly ionic M–CH3 relative to M–CF3, whereas for the predominantly covalent group 8 analogues, π-back-bonding helps to shorten the predominantly covalent M–CF3 relative to M–CH3. The bonding analysis suggests that the significant elongation of C–F bonds α to metals is mainly a consequence of the electropositivity of the group 4 metal centers, with minor, if any, contributions from π-effects; the bond-lengthening effect is most pronounced at the α-position and decays rapidly on moving away from the metal.

Solid‐phase Extraction Coupled Simple On‐line Derivatization Gas Chromatography – Tandem Mass Spectrometry for the Determination of Benzophenone‐type UV Filters in Aqueous Samples

AbstractThe rapid determination of three benzophenone‐type UV filters: 2‐hydroxy‐4‐methoxy‐benzophenone (BP‐3), 2,4‐dihydroxybenzophenone (BP‐1) and 2,2′‐dihydroxy‐4‐methoxy‐benzophenone (BP‐8), in aqueous samples is described. The method involved the extraction of an aqueous sample using an Oasis HLB solid‐phase extraction (SPE) cartridge, followed by on‐line derivatization gas chromatography ‐ tandem mass spectrometry (GC‐MS/MS) with a trimethylsilylating (TMS) reagent. This eco‐friendly, injection‐port derivatization method, is sensitive, rapid, and provides reproducible results for these hydroxylated benzophenones in aqueous samples. The limits of quantitation (LOQs) were determined to be 1.0 to 2.5 ng/L for samples in 100 mL of water. The precision for these analytes, as indicated by relative standard deviations (RSDs), proved to be less than 11% for both intra‐ and inter‐day analysis. Accuracy, expressed as the mean extraction yield, was between 80 and 106%. The method was then applied to some environmental water samples, river water and samples of effluents from a wastewater treatment plant (WWTP), having the potential to contain BP‐3 and BP‐1.

Improved ultrasonic-based sample treatment for the screening of anabolic steroids by gas chromatography/mass spectrometry

A rapid sample treatment procedure for the gas chromatography/mass spectrometry (GC/MS) determination of anabolic steroids in human urine has been developed. The new procedure makes use of ultrasonic energy to reduce reaction times and increase the overall sensitivity. The following variables affecting the performance of the ultrasonic treatment were optimised: (i) time, (ii) device, (iii) frequency, and (iv) temperature. It was found that, under an ultrasonic field, the hydrolysis of conjugated steroids with beta-glucuronidase from Escherichia coli K12 was possible with a treatment time of 10 min. The accuracy and precision of the ultrasonic method were found to be in agreement with those achieved with the conventional thermal conductivity procedure (Student's t-test; p = 0.05, n = 10). After the enzymatic hydrolysis, the derivatisation of the target compounds with trimethylsilyl (TMS) reagent, methyl-N-trimethylsilyltrifluoroacetamide (MSTFA)/NH(4)I/dithioerythritol (DTE) (1000:2:4, v/w/w), was also accelerated using ultrasonic energy. In order to test the applicability of the use of ultrasonic energy in the acceleration of the derivatisation reaction with TMS, the classic method of thermal conductivity was applied for comparative purposes to a pool of 35 androgenic anabolic steroids (AAS) and/or their metabolites. The results demonstrated that after 3 min of sonication in a Sonoreactor device (50% amplitude), 19 of the 35 compounds studied showed similar reaction yield to those obtained with the classic procedure requiring 30 min (Student's t-test; p = 0.05, n = 5); 13 increased to higher silylation yields; and for the steroids 1-testosterone, danazol and etiocholanolone-D5, the same results were obtained using a sonication time of 5 min.The overall applicability of the ultrasonic-based sample treatment method is shown by the analysis of five urine samples. The results are similar to those achieved by the routine procedure. The new method is fast, robust, and allows high sample throughput.

Organometallic uranium(iv) fluoride complexes: preparation using protonolysis chemistry and reactivity with trimethylsilyl reagents

Reaction of the uranium alkyl complex (C(5)Me(5))(2)UMe(2) (1) with Et(3)N.3HF in toluene in the presence of a donor ligand (pyridine or trimethylphosphine oxide) results in gas evolution and the formation of the uranium(IV) difluoride complexes (C(5)Me(5))(2)UF(2)(L) (L = NC(5)H(5) (2), Me(3)P=O (3)). Similarly, reaction of (C(5)Me(5))(2)U[kappa(2)-(C,N)-CH(2)Si(CH(3))(2)N(SiMe(3))] (5) with Et(3)N.3HF in toluene gives the uranium(IV) amide-fluoride complex (C(5)Me(5))(2)U[N(SiMe(3))(2)](F) (6). The fluoride complex (C(5)Me(5))(2)UF(2)(NC(5)H(5)) (2) shows versatile reaction chemistry with a variety of trimethylsilyl reagents and demonstrates that the U-F bond provides an attractive synthetic strategy for accessing new functional groups that are not available from alkoxide or chloride complexes.

Quantitative analysis of ezetimibe in human plasma by gas chromatography‐mass spectrometry

A new, specific and sensitive GC-MS method with electron impact ionization technique was developed for quantitative analysis of ezetimibe (EZE) in human plasma. Prior to GC analysis, EZE was derivatized with N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA), which is a trimethyl silylating reagent. The derivatization reaction was optimized and parameters such as catalyst, derivatization time, temperature, solvent and the volume of silylating reagent were investigated. Trimethylsilyl ether derivative of EZE was determined in selected ion monitoring (SIM, mass-to-charge ratio (m/z): 326) mode. The method was validated with respect to LOD and LOQ, precision, accuracy, linearity, specificity, stability, and recovery. The LOQ and LOD were found as 15 and 10 ng/mL, respectively. The linearity of the method ranged from 15 to 250 ng/mL. The correlation coefficient of the calibration curve was 0.9977 +/- 0.0004 (+/- S.E.M.). The intra- and inter-day precisions (RSD) were less than 6% and accuracies (bias) for intra- and inter-day accuracy were found between -4.04 and 9.71% at four different concentration levels (15, 40, 100, 250 ng/mL). The proposed method was successfully applied to real human plasma samples for determination of total EZE.

Highly efficient synthesis of functionalized tertiary alcohols catalyzed by potassium alkoxide–crown ether complexes

A highly efficient Mukaiyama aldol reaction between ketones and trimethylsilyl enolates in the presence of potassium alkoxide–crown ether complexes as Lewis base catalysts (0.3–5 mol %), which minimized the competing retro-aldol reaction, was developed. These catalysts promoted other addition reactions of trimethylsilyl reagents to ketones and aldimines, such as silyltrifluoromethylation, silylcyanation, and silylphosphonylation. A direct hydrophosphonylation of ketones also proceeded when the catalysts were used as a Brønsted base under mild reaction conditions.

Determination of 24S-Hydroxycholesterol in Human Cerebrospinal Fluid by Gas Chromatography/Mass Spectrometry

A simple pretreatment method for the determination of 24S-hydroxycholesterol in human cerebrospinal fluid by gas chromatography/mass spectrometry (GC/MS) has been developed. Esterified cholesterol was saponified by a high concentration of potassium hydroxide (25 M, 1 mL) in a small volume (10 mL) of a conical test tube with a stopper made of glass. Next, free cholesterol was extracted with a small volume of n-hexane. The combined extracts obtained by the twice extraction were then applied on a silica cartridge for solid-phase extraction. A slight amount of 24S-hydroxycholestertol was separated from a large amount of cholesterol using n-hexane and ethylacetate as an elution solvent. 24S-hydroxycholestertol and 27-hydroxycholesterol-26,26,26,27,27-D5 as an internal standard were converted to trimethylsilyl ethers by the trimethylsilyl (TMS) reagent, and then the TMS derivatives were determined by GC/MS. The method was successfully applied to the determination of 24S-hydroxycholestertol in human cerebrospinal fluid from patients of non-neurodegenerative disorders. The pretreatment method reported here was simple and useful for one multi-specimen material pretreatment.

Quantification of Lorazepam and Lormetazepam in Human Breast Milk Using GC-MS in the Negative Chemical Ionization Mode

Lormetazepam (Loramet is a benzodiazepine mainly used as an hypnotic to treat insomnia. Lorazepam (Temesta) is used as an anxiolytic, tranquilizer, sedative, and anticonvulsant, and it is the major metabolite of lormetazepam. In this study, we designed a method to simultaneously detect and quantify these substances in human breast milk. Solid-phase extraction of 2 mL of milk was followed by derivatization with a trimethylsilyl reagent. Separation and detection was performed using gas chromatography coupled to mass spectrometry in the negative chemical ionization mode. Calibration curves were linear in the ranges of 10-200 and 1-20 ng/mL for lorazepam and lormetazepam, respectively. Limits of detection were estimated at 0.016 ng/mL for lormetazepam and 0.100 ng/mL for lorazepam. Our method was applied to real case samples from a woman receiving both benzodiazepines. Lorazepam concentrations varied from 55.3 to 123.1 ng/mL, and lormetazepam concentrations varied from 1.7 to 7.3 ng/mL.

Evaluation of N-methyl-N-tert-butyldimethylsilyl trifluoroacetamide for environmental analysis under both EIMS and electron capture NICIMS conditions and comparison to trimethylsilyl reagents under EIMS

N-Methyl-N-tert-butyldimethylsilyltrifluoroacetamide (MTBSTFA) is a silylating agent with a range of applicability in clinical and environmental analysis, particularly when substrates possess at least moderate acidity. In this paper, we demonstrate its applicability and limitations as a reagent for environmental analysis by comparing and contrasting two different target analyte problems in a sewage effluent matrix. In one case, electron ionization was used for the determination of three potential endocrine disrupting compounds: 17β-oestradiol, ethynyl oestradiol, and oestrone where the phenolic functionality was silylated with MTBSTFA and compared with results using N,O-bis(trimethylsilyl)-trifluoroacetamide (BSTFA) as the reagent. In this instance, a large volume of effluent was subjected to either solid-phase extraction followed by cleanup using high-performance gel permeation chromatography (AppI) or liquid/liquid extraction followed by SPE fractionation and HPLC fractionation (AppII). The method using BSTFA rather than MTBSTFA was demonstrated to work down to low and sub-ppt levels where the target compounds were found. In a parallel and contrasting study, sewage effluent was analysed for 3,5,6-trichloropyridinol (TCP) by extracting one liter of water using liquid–liquid extraction and determined by GC/MS operated in the negative ion chemical ionization (electron capture) mode after derivatization with MTBSTFA. TCP is the major metabolite of the commonly used insecticide, chlorpyrifos, and herbicide trichlorpyr. The recoveries using dichloromethane as the extractant were 59%, with a relative standard deviation of 2%. This method was used to investigate levels of TCP in sewage effluent. During this analysis, a tentatively identified additional isomer of TCP (X-TCP) was found. The 3,5,6-TCP, the common chlorpyrifos metabolite and the synthesized isomer, 3,4,5-TCP were compared with X-TCP. All three isomers have significantly different retention times. The average level of 3,5,6-TCP was 3.4 ng L−1, while the level of X-TCP was 39.8 ng L−1. The two approaches are compared and contrasted with respect to artefact formation and matrix component effects. The reagent MTBSTFA is found to be suitable for quantitative analysis of environmental samples for relatively acidic substrates (e.g. phenols and carboxylic acids). More powerful silylating agents such as N-methyl-N-trimethylacetamide or BSTFA are required for sterols and similar substrates. The stability of the two silylating reagents appears to be similar and practical for accurate quantitative analysis. Differences in EI spectra with respect to fragmentation may also dictate which reagent is preferred.