Sold under the brand name of Viracept, produced by Roche, exactly where an error in production generated?2013 American Chemical SocietyTelevated levels of sulfonate esters in the final item, which was subsequently withdrawn in the European markets.12 The threshold limit applied to sulfonate esters has led towards the improvement of quite a few analytical approaches for the determination of these GTIs.13 One of the most broadly used approach is gas chromatography (GC) combined with mass spectrometry (MS)14,15 or flame ionization detection (FID). 16 The derivatization of sulfonate esters prior to headspace GCMS,17,18 and sample preconcentration working with solid phase microextraction (SPME)19 have also been employed to achieve the levels of sensitivity required. Other approaches include liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/ MS).20-22 The capability to accurately detect the sulfonate esters is limited by their relative stability, because the compounds might degrade for the duration of sample preparation, leading to poor analytical sensitivity; hence, speedy detection of those compounds is advantageous. To date, the application of direct analysis tactics for the determination of GTIs in pharmaceutical formulations has received little consideration. The mesylate, besylate, and tosylate sulfonates are low-molecular-weight compounds with boiling points that are generally beneath 200 , indicating that thermal desorption (TD) may very well be employed as a probable sampling mechanism. The prospective of GTI detection by direct evaluation was lately demonstratedReceived: April ten, 2013 Accepted: June ten, 2013 Published: June 10,dx.doi.org/10.1021/ac401054n | Anal. Chem. 2013, 85, 6224-Analytical Chemistry in 2011 by McCullough et al., making use of on the internet extractive electrospray (EESI) sampling from a heated reaction mixture, where codeine was made use of as a surrogate GTI.23 In this paper, an in-house created and constructed TD probe capable of heating solid and liquid samples to temperatures in excess of 350 was interfaced to a quadrupole-time-of-flight-mass (Q-ToF) spectrometer. The desorbed methyl p-toluenesulfate ester (MTS) vapor was detected as a sodium salt adduct ionized by extractive electrospray24 inside the presence of 0.01 M sodium acetate. This novel method for the direct detection of MTS within a surrogate API mixture (starch) is demonstrated to levels under a TTC of 1.Silver(I) carbonate Chemscene 5 g/g necessary by the FDA and EMA regulatory bodies.947275-74-3 Chemscene Technical NoteEXPERIMENTAL SECTION Chemical substances.PMID:23460641 Analytical-grade water and methanol have been purchased from Fisher Scientific (Loughborough, U.K.). HPLC grade formic acid, sodium acetate (99.0 ), methyl p-toluenesulfonate (97.0 ) and potato starch had been bought from Sigma-Aldrich (Gillingham, U.K.). All chemical substances have been made use of devoid of further purification. AP/TD Probe. A schematic diagram on the ion supply region of a Waters Synapt HDMS spectrometer (Waters, Manchester, U.K.) modified for AP/TD-EESI-MS is shown in Figure 1. Thelow volumes within a f ume hood, working with suitable personal protection.] This was performed by incineration. Inside the TD experiments, MTS requirements had been placed in to the sample holder and immediately introduced in to the ion supply. For surrogate API experiments, 10 L of regular solution was added to 50 mg of starch, equivalent to concentrations inside the range 0.1-2 ppm (w/w), applying aluminum foil sample wraps which had been ready before analysis and placed in to the sample holder. A compact hole was made within the alumin.