Babiker El-Haj

GC-MS detection and characterization of thebaine as a urinary marker of opium use

The differentiation between legal and illegal opiate product use through the detection of marker compounds in urine is one of the most important subjects in forensic toxicology. Thebaine, an opium alkaloid, can be detected by gas chromatography-mass spectrometry (GC-MS) and has been suggested as a good marker of poppy seed use in differentiation from that of illicit heroin. In the present study, thebaine was targeted as a urinary marker of opium use because it is a major constituent of opium. Although thebaine lacks the conventional functional group, it was found to form a trimethylsilyl (TMS) derivative. This has made it possible to simultaneously detect thebaine together with morphine and codeine in the same urine sample to confirm opium use, thus saving time and cost of analysis while using less material. The TMS derivatization was found to enhance the stability and chromatographic properties of thebaine and to increase the sensitivity of its detection about 50-fold in comparison with that of the underivatized compound. Using the present method, thebaine was analyzed for a number of actual urine samples obtained from users of opium, illicit heroin, or codeine preparation. The results showed that thebaine is a useful opium-use marker subject to its oral administration.

Oripavine as a new marker of opiate product use

During our extensive surveillance of opiates in urine specimens of opium users, we noticed the appearance of an unknown peak (compound X) in total ion chromatograms obtained by gas chromatography-mass spectrometry (GC–MS) after enzymatic hydrolysis and trimethylsilyl (TMS) derivatization. We identified the compound X as oripavine. Oripavine was found to be a new and useful putative marker of opium/poppy seed use in differentiation from heroin, pharmaceutical codeine, and pharmaceutical morphine use. The presence of oripavine in the urine of opium users is probably the result of O-demethylation of the opium alkaloid thebaine. Analytical method optimization for GC–MS detection of oripavine in urine was also undertaken. Underivatized oripavine could not be detected by GC–MS, and trials for derivatization of oripavine with acetic anhydride and propionic anhydride were unsuccessful. Trials were successful with bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane. It was also disclosed that almost all amounts of oripavine in human urine existed in the unconjugated form; it was absolutely necessary to hydrolyze the conjugate before TMS derivatization of oripavine for its GC–MS analysis.

GC-MS detection and tentative characterization of two noscapine metabolites in human urine and their potential as markers for opium and illicit heroin use

Urine samples for cases of drug abuse are regularly screened by gas chromatography-mass spectrometry (GC-MS) after enzyme hydrolysis, liquid-liquid extraction, and trimethylsilyl (TMS) derivatization. During such routine analysis, two compounds (labeled as X1 and X2) were detected in urine samples of opium and illicit heroin users as their TMS derivatives, which led us to tentatively characterize the compounds. It was found that the compounds were noscapine metabolites as determined by GC-MS in both electron-impact ionization (EI) and chemical ionization modes. Together with the analysis of fragment ions in the EI mass spectra, the X1 and X2 compounds were further assigned as 6,7-dihydroxynoscapine and its desmethyl product at either position 6′ or 7′, respectively. The two tentatively characterized compounds were found to be useful as markers for excluding medicinal morphine use and for refuting claims of codeine use or Golden-Seal preparation use often made by heroin addicts to evade conviction. By addition of the above two metabolites, the arsenal of markers for opium and illicit heroin use has now been strengthened.

Linking Aromatic Hydroxy Metabolic Functionalization of Drug Molecules to Structure and Pharmacologic Activity

Drug functionalization through the formation of hydrophilic groups is the norm in the phase I metabolism of drugs for the modification of drug action. The reactions involved are mainly oxidative, catalyzed mostly by cytochrome P450 (CYP) isoenzymes. The benzene ring, whether phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand, the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e., the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e., the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retention, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues are presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design, and drug development.

DEVELOPMENT AND EVALUATION OF HERBAL EXTRACT CREAM FOR HYDRATION AND PHOTO-PROTECTION

DEVELOPMENT AND EVALUATION OF HERBAL EXTRACT CREAM FOR HYDRATION AND PHOTO-PROTECTION Heyam S Ali , Rasha Saad , Sorour Mustafa Alahmed , Najla A.G. Shaheeb , Babiker M. Elhaj 4 Department of Pharmaceutics, Dubai Pharmacy College, Dubai, United Arab Emirates 2 College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia Department of Pharmacognosy, Dubai Pharmacy College, Dubai, United Arab Emirates Ajman University, Shāriqah, United Arab Emirates

Experience of Dubai Pharmacy College with PBL through Students’ Perception

Background: Problem-based learning (PBL) is a student-centered, self-directed and collaborative learning method. The implementation of problem-based learning started in 1969 and has spread since then throughout different parts of the world with variations in its implementation. In spite of its growth and advantages, there is continuing debate about its effectiveness over the conventional teaching learning methods. In Dubai Pharmacy College (DPC), the Bachelor pharmacy program follows 4-year integrated curriculum. The instructional delivery uses traditional lectures, tutorials, quiz, tests and exams and recently implemented PBL since 2008. This study was to explore the perception of DPC students about PBL sessions. Objective: The objectives of the study were: (i) To facilitate the development of key professional competencies and (ii) To identify problems associated with implementation of the program and attempt to provide solutions with new learning tools. Methodology: The students’ perception was examined and assessed using a 5-point Likert scale questionnaire. Results: This questionnaire based cross sectional descriptive study was carried out on 170 out of 202 (84.1 %) who participated in PBL sessions. DPC found PBL session interesting and beneficial. Most students reported their participation in discussion during PBL sessions but the level of participation varied. Some of them worked hard to prepare themselves for discussion while others were relatively passive. Conclusion: PBL helped them with in-depth understanding of certain topics and link their basic science knowledge to clinical classes. They felt that guidance from subject specialists and well prepared facilitators of the sessions were beneficial. The students believed that repetition of triggers from year to year discouraged their active search for learning issues. Majority of the students were undecided or disagreed about the availability of adequate learning resources for their self-study. Reviewing and renewing the PBL triggers, providing guidelines for searching for resource materials and briefing the students and facilitators about the philosophy and principles of principles of PBL sessions more beneficial. Key words: Dubai Pharmacy College, Students Perception, Problem-Based Learning Session, Pharmacy.

Antioxidant assessment on promethazinr HCl decomposition using RP-HPLC assay method

The objective of this study was to investigate the effect of different sodium metabisulfite (SMBS) concentrations under a variety of ICH recommended test conditions. An attempt was made to test the feasibility of increasing shelf life when stored under different conditions. The promethazine hydrochloride (HCL) sample solutions used according to USP 24 and BP 1999 were prepared using different concentration of sodium metabisulfite as antioxidant. Standard solution was prepared using reference promethazine and analyses were done by employing reversed-phase high-performance liquid chromatography (RP-HPLC). The method used is efficient in acceptable resolution. The effect of different concentrations of SMBS on promethazine was investigated in promethazine HCL degradation. Chemical and physical stability was conducted in different conditions. The result shows that the drug was liable to degradation in basic pH medium condition, though the extent of degradation varied. Separation of the drug and the degradation products under various conditions was successfully achieved. The method was validated and the response was linear (r=0.9998) in the drug concentration range of 5 to 50 μg. The mean values (±RSD) of slope and intercept were 46376 (±0.006975) and 200049 (±0.4009), respectively. The recovery of the drug ranged between 98.3 and 101.16% from the mixture of degradation products. SMBS concentration influences the degradation process. Increase in concentration resulted in decrease of promethazine degradation. The developed method is simple and accurate in use for analysis of the drug and its degradation products. Antioxidant (SMBS) has important role in preventing promethazine degradation beside other factors. Key words: Degradation, reversed-phase high-performance liquid chromatography (RP-HPLC), promethazine hydrochloride, sodium metabisulfite.

GC-MS detection and characterization of two laudanosine metabolites in urine as probable markers of atracurium administration

mentations, while the CI mass spectra exhibited both the protonated molecular ions and intense fragment ions (corresponding to base-peak ions in EI spectra) after TMS derivatization. However, the mass spectral libraries of both the National Institute of Standards and Technology (NIST) and Wiley characterized underivatized compound X1 as 1,2,3,4-tetrahydroisoquinoline6,7-dimethoxy-1-phenmethanol-2-methyl (TDPM) with match qualities of 96%. Nonetheless, this compound was excluded as a possible assignment of compound X1 based on the difference in molecular weights [313 for TDPM and 343 for X1 (Table 1)]. As can be deduced from the library match for compound X1 (i.e., TDPM) and as has been previously found for methyl-derivatized reticuline [1], the basepeak ions in EI-MS and intense fragment-peak ions in CI-MS, both of m/z 206 (Table 1), must have come from the dimethoxy-N-methyl-tetrahydroisoquinoline moiety (Fig. 1). The substantial similarities of the GC-MS data of compounds X1 and X2 to those of reticuline [1] offered the lead for their chemical structure elucidation. In reticuline (Fig. 1) characterization [1], the masses of 151 and 264 have been attributed to dimethoxybenzyl and methoxy-trimethylsilyloxy-N-methyl-tetrahydroisoquinoline moieties, respectively. Because the same values were observed for compound X2 and their sum accounts for the observed and calculated molecular weight of 415 (Table 1, Fig. 1), compound X2 can be assigned the chemical structure shown in Fig. 1 and given the chemical name 6-(or 7-)desmethyllaudanosine. Similarly, the masses of 137 and 209 observed for compound X1 (Table 1) could be associated with hydroxy-methoxybenzyl and methoxy-trimethylsilyloxy-benzyl moieties, respectively (Fig. 1). These masses (i.e., 137 and 209) together with the m/z 206 (which corresponds to Received: 20 June 2007 / Accepted: 16 August 2007 / Published online: 1 November 2007

False-negative results for bromazepam use observed by the EMIT II Plus benzodiazepine assays

During our extensive routine analyses of drugs of abuse and other drugs such as benzodiazepines using both immunoassays and gas chromatography-mass spectrometry (GC-MS), we have noticed that the EMIT II benzodiazepine assays for urine samples sometimes gave false-negative results for bromazepam use or abuse. The negative benzodiazepine immunoassays and positive GC-MS results for bromazepam in urine could be explained by the absence (or below the detection limit) of 3-hydroxybromazepam (3HB) and the presence of 2-amino-3-hydroxy-5-bromobenzoylpyridine (AHBBP), which are the two major metabolites of bromazepam. 3HB cross-reacted with the antibody contained in the EMIT II, but AHBBP did not, due to their structural characteristics. To avoid such false-negative results for bromazepam, AHBBP screening by GC-MS is recommended. The false-negative results observed for bromazepam are probably not limited to the EMIT II kit; the same phenomena may be also true for other commercially available kits that are based on immunochemical reactions.