Emad L. Izake

Forensic and homeland security applications of modern portable Raman spectroscopy.

Modern detection and identification of chemical and biological hazards within the forensic and homeland security contexts may well require conducting the analysis in field while adapting a non-contact approach to the hazard. Technological achievements on both surface and resonance enhancement Raman scattering re-developed Raman spectroscopy to become the most adaptable spectroscopy technique for stand-off and non-contact analysis of hazards. On the other hand, spatially offset Raman spectroscopy proved to be very valuable for non-invasive chemical analysis of hazards concealed within non-transparent containers and packaging.

Spatially offset Raman spectroscopy (SORS) for the analysis and detection of packaged pharmaceuticals and concealed drugs

Spatially offset Raman spectroscopy (SORS) is a powerful new technique for the non-invasive detection and identification of concealed substances and drugs. Here, we demonstrate the SORS technique in several scenarios that are relevant to customs screening, postal screening, drug detection and forensics applications. The examples include analysis of a multi-layered postal package to identify a concealed substance; identification of an antibiotic capsule inside its plastic blister pack; analysis of an envelope containing a powder; and identification of a drug dissolved in a clear solvent, contained in a non-transparent plastic bottle. As well as providing practical examples of SORS, the results highlight several considerations regarding the use of SORS in the field, including the advantages of different analysis geometries and the ability to tailor instrument parameters and optics to suit different types of packages and samples. We also discuss the features and benefits of SORS in relation to existing Raman techniques, including confocal microscopy, wide area illumination and the conventional backscattered Raman spectroscopy. The results will contribute to the recognition of SORS as a promising method for the rapid, chemically specific analysis and detection of drugs and pharmaceuticals.

Spectrophotometric and fluorimetric determination of diazepam, bromazepam and clonazepam in pharmaceutical and urine samples

New spectrophotometric and fluorimetric methods have been developed to determine diazepam, bromazepam and clonazepam (1,4-benzodiazepines) in pure forms, pharmaceutical preparations and biological fluid. The new methods are based on measuring absorption or emission spectra in methanolic potassium hydroxide solution. Fluorimetric methods have proved selective with low detection limits, whereas photometric methods showed relatively high detection limits. Successive applications of developed methods for drugs determination in pharmaceutical preparations and urine samples were performed. Photometric methods gave linear calibration graphs in the ranges of 2.85-28.5, 0.316-3.16, and 0.316-3.16 microgml-1 with detection limits of 1.27, 0.08 and 0.13 microgml-1 for diazepam, bromazepam and clonazepam, respectively. Corresponding average errors of 2.60, 5.26 and 3.93 and relative standard deviations (R.S.D.s) of 2.79, 2.12 and 2.83, respectively, were obtained. Fluorimetric methods gave linear calibration graphs in the ranges of 0.03-0.34, 0.03-0.32 and 0.03-0.38 microgml-1 with detection limits of 7.13, 5.67 and 16.47 ngml-1 for diazepam, bromazepam and clonazepam, respectively. Corresponding average errors of 0.29, 4.33 and 5.42 and R.S.D.s of 1.27, 1.96 and 1.14 were obtained, respectively. Statistical Students t-test and F-test have been used and satisfactory results were obtained.

Potentiometric determination of some 1,4-benzodiazepines in pharmaceutical preparations and biological samples

Abstract New, simple, low cost and sensitive ion-selective electrodes are described for the determination of some 1,4-benzodiazepines in their pharmaceutical preparations as well as in biological fluids. Drug-tetraphenylborate and drug-phosphotungstate ion pairs have been prepared and used as electroactive materials. Poly(vinyl chloride) (PVC), and poly(esterurethane)s (UPCLs, UPBA, and UPDEGA) are used as the matrix. The proposed sensors give rapid Nernstian responses for 10−4–10−6 M of the abovementioned drugs in a pH range of 3–7. The membranes developed have potential stability for up to 4 weeks and show high selectivity for the investigated drugs over many interfering ions. The electrodes are used for determining trace amounts of bromazepam, clonazepam and diazepam in their pharmaceutical preparations as well as in biological fluids. For pharmaceutical preparations, the relative standard deviation (RSD) values were in the range, 1.37–4.1, 0.7–2.52 and 0.3–1.2% for bromazepam, clonazepam and diazepam, respectively using the PVC based electrodes, while for the UPBA based electrodes, the (RSD) values were in the range 0.6–3.35, 0.7–2.45 and 0.6–2.41%. For biological samples, the RSD values were 0.64–1.88, 0.37–1.8 and 1.36–3.57% for bromazepam, clonazepam and diazepam, respectively. Comparison of the results obtained using the proposed electrodes with those found using a (HPLC) reference method showed that the ion-selective electrode technique is sensitive, reliable and can be used with very good accuracy and high % recovery without pretreatment procedures of the samples to minimize interfering matrix effects.

Noninvasive, Quantitative Analysis of Drug Mixtures in Containers Using Spatially Offset Raman Spectroscopy (SORS) and Multivariate Statistical Analysis

In this paper, spatially offset Raman spectroscopy (SORS) is demonstrated for noninvasively investigating the composition of drug mixtures inside an opaque plastic container. The mixtures consisted of three components including a target drug (acetaminophen or phenylephrine hydrochloride) and two diluents (glucose and caffeine). The target drug concentrations ranged from 5% to 100%. After conducting SORS analysis to ascertain the Raman spectra of the concealed mixtures, principal component analysis (PCA) was performed on the SORS spectra to reveal trends within the data. Partial least squares (PLS) regression was used to construct models that predicted the concentration of each target drug, in the presence of the other two diluents. The PLS models were able to predict the concentration of acetaminophen in the validation samples with a root-mean-square error of prediction (RMSEP) of 3.8% and the concentration of phenylephrine hydrochloride with an RMSEP of 4.6%. This work demonstrates the potential of SORS, used in conjunction with multivariate statistical techniques, to perform noninvasive, quantitative analysis on mixtures inside opaque containers. This has applications for pharmaceutical analysis, such as monitoring the degradation of pharmaceutical products on the shelf, in forensic investigations of counterfeit drugs, and for the analysis of illicit drug mixtures which may contain multiple components.

Characterization of reaction products and mechanisms in atmospheric pressure plasma deposition of carbon films from ethanol

Atmospheric pressure plasma deposition (APPD) of carbon films from a predominantly ethanol liquid phase was carried out under varying experimental conditions. A solid precipitate formed in the process was characterised by FT-IR and Raman spectroscopy. After each experiment the liquid phase was analysed for by-products by GC-MS. A number of compounds were found and mechanisms for their formation are proposed. These mechanisms involve the production of free radical species under the high energy plasma/discharge conditions of the process. The formation of groups of compounds was found to correlate with the voltage in the cell, but not with any other experimental parameter.

DETERMINATION OF BROMAZEPAM AND CLONAZEPAM IN PURE AND PHARMACEUTICAL DOSAGE FORMS USING CHLORANIL AS A CHARGE TRANSFER COMPLEXING AGENT

ABSTRACT Two new spectrophotometric procedures for determining trace amounts of bromazepam and clonazepam, 1,4-benzodiazepine derivatives in their pure and pharmaceutical dosage forms have been developed. The methods are based on forming C.T. complexes with chloranil in chloroform or ethanol at alkaline pH. The absorbance of the formed C.T. complexes were measured at λ = 330 nm and λ = 375 nm for bromazepam and clonazepam, respectively. Linear calibration curves were obtained in the ranges of 31.6–316.0 µg mL−1 for bromazepam and of 63.2–316.0 µg mL−1 for clonazepam. Average recoveries of 99.00–99.60% and 98.57–99.60% were obtained. These reflect 0.5–1.11% and 0.67–1.74% relative errors for bromazepam and clonazepam, respectively. The methods showed standard deviations of 0.6–2.00 and 0.75–1.11 with variance coefficients of 0.63–1.58% and 0.32–1.19% for bromazepam and clonazepam tablets, respectively. Student t-test and F-test statistical treatments were applied for the results obtained by the two methods. t-values indicated the absence of systematic errors at 95% confidence level. Comparing our methods with official HPLC method at 95% confidence level gave insignificant differences. This shows suitability of the two methods for safety, accurate and simple use for quality control analysis of investigated drugs in pure as well as in pharmaceutical preparations.

Standoff Raman spectrometry for the non-invasive detection of explosives precursors in highly fluorescing packaging.

Noninvasive standoff deep Raman spectroscopy has been utilised for the detection of explosives precursors in highly fluorescing packaging from 15m. To our knowledge this is the first time standoff deep Raman spectroscopy of concealed substances in highly fluorescing coloured packaging is demonstrated. Time-resolved Raman spectroscopy, spatially offset Raman spectroscopy and time-resolved spatially offset Raman spectroscopy have been compared to identify their selectivity towards the deep layers of a sample. The selectivity of time-resolved Raman spectroscopy towards the concealed chemical substances was found to be comparable to that of spatially offset Raman spectroscopy. However, time-resolved Raman spectroscopy did not require precise translation of the laser excitation beam onto the surface of the interrogated packaging as in the case of spatially offset Raman spectroscopy. Our results confirm that standoff time-resolved spatially offset Raman spectroscopy has significantly higher selectivity towards the deep layers of a sample when compared to the other deep Raman spectroscopy modes. The developed spectrometer was capable of detecting the concealed substances within 5s of data acquisition. By using time-resolved spatially Raman spectroscopy, a Raman spectrum that is representative of the content alone was acquired without the use of sophisticated algorithms to eliminate the spectral contributions of the packaging material within the acquired spectrum as in the case of time-resolved Raman spectroscopy and spatially offset Raman spectroscopy.

Toward non-invasive detection of concealed energetic materials in-field under ambient light conditions

Spatially offset Raman spectroscopy (SORS) is demonstrated for the non-contact detection of energetic materials concealed within non-transparent, diffusely scattering containers. A modified design of an inverse SORS probe has been developed and tested. The SORS probe has been successfully used for the detection of various energetic substances inside different types of plastic containers. The tests have been successfully conducted under incandescent and fluorescent background lights as well as under daylight conditions, using a non-contact working distance of 6 cm. The interrogation times for the detection of the substances were less than 1 minute in each case, highlighting the suitability of the device for near real-time detection of concealed hazards in the field. The device has potential applications in forensic analysis and homeland security investigations.

Real-time detection of concealed chemical hazards under ambient light conditions using Raman spectroscopy

Current concerns regarding terrorism and international crime highlight the need for new techniques for detecting unknown and hazardous substances. A novel Raman spectroscopy‐based technique, spatially offset Raman spectroscopy (SORS), was recently devised for noninvasively probing the contents of diffusely scattering and opaque containers. Here, we demonstrate a modified portable SORS sensor for detecting concealed substances in‐field under different background lighting conditions. Samples including explosive precursors, drugs, and an organophosphate insecticide (chemical warfare agent surrogate) were concealed inside diffusely scattering packaging including plastic, paper, and cloth. Measurements were carried out under incandescent and fluorescent light as well as under daylight to assess the suitability of the probe for different real‐life conditions. In each case, it was possible to identify the substances against their reference Raman spectra in less than 1 min. The developed sensor has potential for rapid detection of concealed hazardous substances in airports, mail distribution centers, and customs checkpoints.