Beta-adrenergic receptor agonists are growth-promoting drugs with the potential for illegal use in livestock, and human toxicity has resulted from consumption of contaminated meat. On-line liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) was used for sensitive detection of several beta-agonists in retina, a tissue reported to concentrate and retain such residues for extended periods. Multiresidue extraction, separation, detection, and confirmation procedures were developed for retinal tissue and applied to eyes from cattle treated with clenbuterol (69-201 ppb) and to control eyes spiked with salbutamol (100 ppb) and terbutaline (25-100 ppb). Rapid switching of the potential difference between sampling cone and skimmer in the transport region of the API source was used to optimize acquisition of the protonated molecules and characteristic fragment ions obtained by collision-induced dissociation reactions. The respective selected ions were simultaneously acquired using a single quadrupole mass spectrometer. The accurate and precise agreement observed for diagnostic ion intensity ratios between beta-agonists in retinal samples and authentic standards suggests that LC/APCI-MS can be used for confirmation of analyte structure at trace levels and does not require the use of a triple-stage quadrupole mass analyzer.
A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head comparison with electrospray ionization (ESI) on the same high-resolution MS system. The atmospheric pressure ionization source is composed of a grounded nebulizer spraying onto a high voltage, cylindrical stainless steel target. Molecules are ionized in a similar fashion to electrospray ionization, predominantly producing protonated or deprotonated species. Adduct formation (e.g., proton and sodium adducts) and in-source fragmentation is shown to be almost identical between the two sources. The performance of the new API source was compared with electrospray by infusion of a mix of 22 pharmaceutical compounds with a wide variety of functional groups and physico-chemical properties (molecular weight, logP, and pKa) in more than 100 different conditions (mobile phase strength, solvents, pH, and flow rate). The new API source shows an intensity gain of a factor 2.2 compared with ESI considering all conditions on all compounds tested. Finally, some hypotheses on the ionization mechanism, similarities, and differences with ESI, are discussed. Graphical Abstract ᅟ.
Methylphenidate (MP, Ritalin) is a psychotropic drug widely prescribed to children for treating the symptoms of attention deficit disorder with and without hyperactivity. Because little information exists about the effects of chronic MP administration on cognitive function in children, measures of behavior changes in non-human primates are important surrogates. An essential component of such studies is the determination of MP plasma levels under chronic and acute dosing conditions. An analytical method was developed that provided sufficient sensitivity to measure low levels of the active parent drug (lower limit of quantitation = 0.25 ng/mL) and the inactive metabolite, ritalinic acid (RA), in monkey plasma as well as the ability to conveniently analyze large numbers of samples. The method uses a polymeric reversed-phase sorbent for solid phase extraction, an efficient reverse-phase high performance liquid chromatography (HPLC) separation, deuterated internal standards for isotope dilution quantification of MP and RA, and detection by sensitive electrospray ionization mass spectrometry (ES-MS) with a single quadrupole instrument. The method responses are linear over the range of plasma concentrations of MP and RA observed in monkeys, gives respective analyte recoveries of 75 and 60% with reasonable precision and accuracy, and demonstrates robust MS performance for rapid determination of MP/RA plasma levels. The average peak MP concentration (ca. 16 ng/mL) and half-lives for MP and RA elimination in monkeys (1.79 and 2.31 h, respectively) were not significantly different under acute vs. chronic dosing conditions and were comparable to values previously reported from human studies.
The
emergence of ambient ionization techniques and their combination
with smaller, cheaper mass spectrometers is beginning to make real
the possibility of mass spectrometry measurements being made routinely
outside of traditional laboratory settings. Here, we describe the
development of an atmospheric solids analysis probe (ASAP) source
for a commercially available miniaturized, single-quadrupole mass
spectrometer and subsequent modification of the instrument to allow
it to run as a deployable system; we further go on to describe the
application of this instrument to the identification of the contents
of drug seizures. For the drug seizure analysis, a small quantity
of the material (powder, tablet, resin, etc.) was dissolved in ethanol
and shaken to extract the analytes, the resulting solutions were then
sampled by dipping a sealed glass capillary into the solution prior
to analysis by ASAP–MS. Identification of the contents of the
seizures was carried out using a NIST searching approach utilizing
a bespoke spectral library containing 46 compounds representative
of those most commonly encountered in UK forensic laboratories. In
order to increase confidence in identification the library sample
and subsequent analyses were carried out using a four-channel acquisition
method; each channel in this method used a different cone voltage
(15, 30, 50, and 70 V) inducing differing levels of in-source fragmentation
in each channel; the match score across each channel was then used
for identification. Using this developed method, a set of 50 real-life
drug samples was analyzed with each of these being identified correctly
using the library searching method.
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