Adam Lanzarotta

A multidisciplinary approach for the analysis of an adulterated dietary supplement where the active pharmaceutical ingredient was embedded in the capsule shell.

Fourier transform infrared (FT-IR) microspectroscopic imaging, Raman microspectroscopy, optical microscopy and high performance liquid chromatography with mass spectrometric (LC/MS) detection were employed to examine a dietary supplement adulterated with an undeclared active pharmaceutical ingredient (API). While a trace level of the API was detected in the capsule contents, a higher concentration of API was found in the capsule shell, which indicated the use of an unconventional manufacturing process to hide the API and thus avoid detection. This study demonstrates the need for a multidisciplinary approach to provide a complete assessment of a suspect adulterated dietary supplement.

Analysis of Counterfeit Pharmaceutical Tablet Cores Utilizing Macroscopic Infrared Spectroscopy and Infrared Spectroscopic Imaging

Advantages and limitations of analyzing authentic and counterfeit pharmaceutical tablets with both macro (nonimaging) attenuated total internal reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and micro ATR-FT-IR spectroscopic imaging have been evaluated. The results of this study demonstrated that micro ATR imaging was more effective for extracting formulation information (sourcing), whereas a macro ATR approach was better suited for counterfeit detection (screening). More importantly, this study demonstrated that a thorough analysis of the counterfeit core can be achieved by combining the results of both techniques.

Prism-Based Infrared Spectrographs Using Modern-Day Detectors

A comparison of prism-based spectrographs to grating-based spectrographs is made when each of the systems is coupled to a modern-day liquid-nitrogen-cooled photovoltaic array detector. A comparison of the systems is also made using a room-temperature microbolometer array detector. Finally, infrared microspectroscopy of samples whose size is ∼10 micrometers will be demonstrated using a prism spectrograph outfitted with both types of detectors. The results of the study show that prism-based spectrographs offer an economical alternative to grating-based systems when spectral coverage is more critical than spectral resolution. The results also demonstrate that spectra with good signal-to-noise ratios can be collected on any of the systems with a total integration time of 10 seconds or less.

Rapid Molecular Imaging Using Attenuated Total Internal Reflection Planar Array Infrared Spectroscopy for the Analysis of Counterfeit Pharmaceutical Tablets

A planar array infrared (PA-IR) spectrograph containing an attenuated total internal reflection (ATR) accessory has been constructed in order to permit rapid analysis of poorly transmitting materials. The technique has been optimized to allow molecular spectroscopic information to be collected in roughly 2 seconds with a corresponding peak-to-peak noise value as low as 2.14 × 10−4 absorbance units. Additionally, up to 150 spectra could be extracted from sample sizes as large as 6 mm where each spatial element measured 40 × 200 μm at the sample position. An application study for this technique entailed developing an embedding method that allows cross-sectioned pharmaceutical tablets to be brought into intimate contact with the internal reflection element (IRE) of the accessory. A supplemental investigation involved calculating the yield strength of multiple IRE materials in order to determine the maximum amount of pressure that can be applied to a sample without damaging the IRE. Finally, feasibility was demonstrated for using the instrument/accessory as a means to rapidly authenticate suspected counterfeit pharmaceutical tablets.

Approximating the Detection Limit of an Infrared Spectroscopic Imaging Microscope Operating in an Attenuated Total Reflection (ATR) Modality: Theoretical and Empirical Results for an Instrument Using a Linear Array Detector and a 1.5 Millimeter Germanium Hemisphere Internal Reflection Element

Theoretical and empirical detection limits have been estimated for aripiprazole (analyte) in alpha lactose monohydrate (matrix model pharmaceutical formulation) using a micro-attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopic imaging instrument equipped with a linear array detector and a 1.5 mm germanium hemisphere internal reflection element (IRE). The instrument yielded a theoretical detection limit of 0.0035% (35 parts per million (ppm)) when operating under diffraction-limited conditions, which was 49 times lower than what was achieved with a traditional macro-ATR instrument operating under practical conditions (0.17%, 1700 ppm). However, these results may not be achievable for most analyses because the detection limits will be particle size limited, rather than diffraction limited, for mixtures with average particle diameters greater than 8.3 μm (most pharmaceutical samples). For example, a theoretical detection limit of 0.028% (280 ppm) was calculated for an experiment operating under particle size-limited conditions where the average particle size was 23.4 μm. These conditions yielded a detection limit of 0.022% (220 ppm) when measured empirically, which was close to the theoretical value and only eight times lower than that of a faster, more simplistic macro-ATR instrument. Considering the longer data acquisition and processing times characteristic of the micro-ATR imaging approach (minutes or even hours versus seconds), the cost-benefit ratio may not often be favorable for the analysis of analytes in matrices that exhibit only a few overlapping absorptions (low-interfering matrices such as alpha lactose monohydrate) using this technique compared to what can be achieved using macro-ATR. However, the advantage was significant for detecting analytes in more complex matrices (those that exhibited several overlapping absorptions with the analyte) because the detection limit of the macro-ATR approach was highly formulation dependent while that of the micro-ATR imaging technique was not. As a result, the micro-ATR imaging technique is expected to be more valuable than macro-ATR for detecting analytes in high-interfering matrices and in products with unknown ingredients (e.g., illicit tablets, counterfeit tablets, and unknown powders).

Forensic Analysis of Human Autopsy Tissue for the Presence of Polydimethylsiloxane (Silicone) and Volatile Cyclic Siloxanes using Macro FT-IR, FT-IR Spectroscopic Imaging and Headspace GC-MS†

This study describes effective and straightforward primary and secondary methods for the detection of silicone in human autopsy tissue. The primary method is polydimethylsiloxane (PDMS) specific and employs either macro‐attenuated total reflection Fourier transform infrared (ATR‐FT‐IR) spectroscopy for samples with a high PDMS concentration (relative to that of the matrix) or micro‐FT‐IR spectroscopic imaging in a reflection/absorption modality for samples with a low PDMS concentration. Although the secondary method is not PDMS specific, it employs headspace gas chromatography with mass spectrometric detection (HS/GC‐MS) for the detection of low molecular weight volatile cyclic siloxanes (VCS), which are characteristic marker compounds for PDMS. Overall, the combined results from the primary and secondary analyses provide reliable evidence for the presence of silicone.

Development and implementation of a pass/fail field-friendly method for detecting sildenafil in suspect pharmaceutical tablets using a handheld Raman spectrometer and silver colloids

HIGHLIGHTSHandheld Raman spectrometers and silver colloids are used to detect sildenafil in suspect tablets.The method is based on a pass/fail platform that can be taught to non‐experts in about 20 min.The method involves measuring sample solutions directly through glass vials (no drying required).The method proved to be 92.6% effective on average for 117 counterfeit and unapproved drugs.The method yielded detection limits in samples as low as 10 ppm. ABSTRACT A simple, fast, sensitive and effective pass/fail field‐friendly method has been developed for detecting sildenafil in suspect Viagra and unapproved tablets using handheld Raman spectrometers and silver colloids. The method involves dissolving a portion of a tablet in water followed by filtration and addition of silver colloids, resulting in a solution that can be measured directly through a glass vial. Over one hundred counterfeit Viagra and unapproved tablets were examined on three different devices during the method development phase of the study. While the pass/fail approach was found to be 92.6% effective on average, the efficacy increased to 97.4% on average when coupled with the softwares “Discover Mode” feature that allows the user to compare a suspect spectrum to that of a stored sildenafil spectrum. The lowest concentration of sildenafil in a water/colloid solution that yielded a “Pass” was found to be 7.6 &mgr;g/mL or 7.6 parts per million (ppm). For the analysis of suspect tablets, this value was found to be as low as 10 &mgr;g/mL and as high as 625 &mgr;g/mL. This variability was likely related to the tablet formulation, e.g., concentration of sildenafil, presence and concentration of water‐soluble and/or water‐insoluble ingredients. However, since most counterfeit Viagra and unapproved tablets contain >50 mg sildenafil per tablet, such low concentrations will not be encountered often. Limited in‐lab and in‐field validation studies were conducted in which analysts/field agents followed the procedure outlined in this study for small sample sets. These individuals were provided with written instructions, a ˜20 min demonstration regarding how to perform the procedure and use the instrument, and a kit with field‐friendly supplies (purified bottled water from a local grocery store, disposable plastic pipettes, eye‐dropper with a silver colloid solution, etc.). The method proved to be 98.3% and 91.7% effective for the in‐lab and in‐field validation studies, respectively, which demonstrated the ruggedness, simplicity and practicality of the method.

Infrared microspectroscopy using prism-based spectrographs and focal plane array detection.

Several prism-based spectrographs employing a mercury cadmium telluride (MCT) focal plane array detector have been interfaced to an infrared microscope. In the combined system, the area-defining aperture of the microscope also served as the entrance slit to the spectrograph. This investigation considered the fundamental limits of diffraction for both the spectrograph and microscope in order to determine both the spatial and spectral resolution of the system as a whole. Experimental results for spectral resolution, spectral range, and peak-to-peak noise have been presented. Finally, the dynamic capabilities of one spectrograph/microscope combination were investigated.

Simultaneous Orthogonal Drug Detection using Fully Integrated Gas Chromatography with Fourier Transform Infrared Detection and Mass Spectrometric Detection.

Analytes that co-elute and yield nearly identical electron ionization (EI) mass spectra, as well as analytes that yield non-specific EI fragmentation patterns, have been identified using fully integrated gas chromatography with direct deposit Fourier transform infrared detection and mass spectrometric detection (GC/FT-IR/MS). While the IR detector proved to be more selective for identifying analytes such as synthetic cannabinoids and weight loss drugs, it was limited by a relatively high detection limit of 8.4 parts per million (ppm) for non-targeted identification of sibutramine based on a single injection but was reduced to 840  parts per billion (ppb) for targeted identification of sibutramine by redepositing ten injections along the same track. The MS detector was less selective for identifying these analytes but yielded non-targeted and targeted detection limits of approximately 84 ppb and 8.4 ppb, respectively, which corresponded to a 100-fold advantage compared to the IR detector. Overall, the results of this study demonstrate that the advantages of each detector compensate for the limitations of the other, which allows a wider range of analytes and concentrations to be examined using a fully integrated GC/FT-IR/MS instrument compared to what can be examined using GC/IR or GC/MS independently. Not only does this approach reduce consumption of laboratory resources and time, it provides IR and MS information on the same sample, which is important for forensic analyses that require data from two or more orthogonal techniques to make an identification.

Analysis of Counterfeit Coated Tablets and Multi-Layer Packaging Materials Using Infrared Microspectroscopic Imaging

An effective method for detecting and characterizing counterfeit finished dosage forms and packaging materials is described in this study. Using attenuated total internal reflection Fourier transform infrared spectroscopic imaging, suspect tablet coating and core formulations as well as multi-layered foil safety seals, bottle labels, and cigarette tear tapes were analyzed and compared directly with those of a stored authentic product. The approach was effective for obtaining molecular information from structures as small as 6 μm.