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PubMed2004

Capillary electrophoresis analysis of a wide variety of seized drugs using the same capillary with dynamic coatings.

Capillary electrophoresis methodology is presented for the routine analysis of a wide variety of seized drugs using the same capillary with dynamic coatings and multiple run buffers. The types of exhibits analyzed using diode array UV detection include phenethylamines, cocaine, oxycodone, heroin, lysergic acid diethylamide (LSD), opium, hallucinogenic mushrooms, and gamma-hydroxybutyrate-gamma-butyrolactone (GHB-GBL). Both qualitative and quantitative analyses are achieved using run buffers that contain additives that provide for secondary equilibrium and/or dynamic coating of the capillary. Dynamic coating of the capillary surface is accomplished by rapid flushes of 0.1 N sodium hydroxide, water, buffer containing polycation coating reagent, and a buffer containing a polyanionic coating reagent (with or without cyclodextrin(s)) or a micelle coating reagent. Dynamic coating with a polyanionic coating reagent is used for the analysis of moderately basic seized drugs and adulterants. The use of cyclodextrin in the run buffer not only allows for chiral analysis but also greatly enhances separation selectivity for achiral solutes. A capillary dynamically coated with a micelle allows for the analysis of neutral, acidic, and weakly basic drugs (GHB, GBL and neutral, acidic, and weakly basic adulterants). Dynamic coating, which gives rise to a relatively high and robust electroosmotic flow at pH < 7, allows for rapid, precise and reproducible separations. For a wide variety of drugs, excellent linearity and migration time precision and good peak area precision (external and internal standard) is obtained. Quantitative results for synthetic mixtures are in good agreement with actual values. Screening for adulterants is greatly enhanced by the use of automated library searches.

Alkaloids↗
PubMed1994

Bilateral intra-accumbens self-administration of d-amphetamine: antagonism with intra-accumbens SCH-23390 and sulpiride.

The efficacy of d-amphetamine to support a selective bilateral intra-accumbens self-administration response was examined. Bilateral intra-accumbens infusions of d-amphetamine were made contingent upon the acquisition of a lever-pressing response. Two identical levers were available within the operant chamber. Depression of the drug lever resulted in the intra-accumbens delivery of 1 microgram d-amphetamine; responses upon the second, control lever were recorded but had no programmed consequences. Animals were not 'primed' with non-contingent infusions of d-amphetamine at any time during these experiments. Nonetheless, animals readily acquired a selective response upon the drug lever. Removal of the d-amphetamine moiety from the infusate resulted in a large decline in responding, and the abolition of the selectivity of the response for the drug lever. Adulteration of the infusate with either the D1 dopamine receptor antagonist SCH-23390 or the D2 dopamine receptor antagonist sulpiride enhanced the rate of response selectively upon the drug lever. Reductions in the dose of d-amphetamine also increased the rate of response. The effect of co-adulteration of the infusate with both SCH-23390 and sulpiride together was purely additive. The implications of these data for the methodology of intracranial drug self-administration, and the relationship between D1 and D2 dopamine receptors within the nucleus accumbens are discussed.

Animals↗
PubMed2002

Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review.

The popularity of Chinese herbal medicines (CHMs) demands a critical analysis of safety issues. The aim of this systematic review is to summarize data regarding adulterations of CHMs with conventional drugs. Literature searches were carried out in six databases. Articles containing original data on adulterations were considered without language restrictions. Eighteen case reports, two case series and four analytical investigations were identified. The list of adulterants contains drugs associated with serious adverse effects like corticosteroids. In several instances, patients were seriously harmed. One report from Taiwan suggests that 24% of all samples were contaminated with at least one conventional pharmacological compound. It is concluded that adulteration of CHMs with synthetic drugs is a potentially serious problem which needs to be addressed by adequate regulatory measures.

Drug Contamination↗
PubMed2004

The detection of drugs of abuse in fingerprints using Raman spectroscopy II: cyanoacrylate-fumed fingerprints.

This paper describes the application of Raman spectroscopy to the detection of exogenous substances in cyanoacrylate-fumed fingerprints. The scenario considered was that of an individual handling a substance and subsequently depositing a contaminated fingerprint. These fingerprints were enhanced by cyanoacrylate fuming, a process in which a layer of white cyanoacrylate polymer is deposited on the fingerprint material, enabling visual detection. Five drugs of abuse (codeine phosphate, cocaine hydrochloride, amphetamine sulphate, barbital and nitrazepam) and five non-controlled substances of similar appearance, which may be used in the adulteration of drugs of abuse (caffeine, aspirin, paracetamol, starch and talc), were used. The substances studied could be clearly distinguished using their Raman spectra and were all successfully detected in cyanoacrylate-fumed fingerprints. Photobleaching was necessary to reduce the fluorescence background in the spectra of some substances. Raman spectra obtained from the substances in cyanoacrylate-fumed fingerprints were of a similar quality to spectra obtained from the substances under normal sampling conditions, however, interfering Raman bands arising from the cyanoacrylate polymer were present in the spectra. In most cases the only interfering band was the C triple bond N stretching mode of the polymer, and there were no cases where the interfering bands prevented identification of the substances. If necessary, the interfering bands could be successfully removed by spectral subtraction. The most difficult aspect of the detection of these substances in cyanoacrylate-fumed fingerprints was visually locating the substance in the fingerprint beneath the polymer layer in order to obtain a Raman spectrum.

Cyanoacrylates↗
PubMed2004

The detection of drugs of abuse in fingerprints using Raman spectroscopy I: latent fingerprints.

This paper describes the application of Raman spectroscopy to the detection of exogenous substances in latent fingerprints. The scenario considered was that of an individual handling a substance and subsequently depositing a contaminated fingerprint. Five drugs of abuse (codeine phosphate, cocaine hydrochloride, amphetamine sulphate, barbital and nitrazepam) and five non-controlled substances of similar appearance, which may be used in the adulteration of drugs of abuse (caffeine, aspirin, paracetamol, starch and talc), were studied in both sweat-rich and sebum-rich latent fingerprints. The substances studied could be clearly distinguished using their Raman spectra and were all successfully detected in latent fingerprints. Photobleaching was necessary to reduce the fluorescence background in the spectra of some substances. Raman spectra obtained from the substances in sweat-rich latent fingerprints were of a similar quality to spectra that obtained from the substances under normal sampling conditions. Interfering Raman bands arising from latent fingerprint material were present in the spectra obtained from the substances in sebum-rich fingerprints. These bands did not prevent identification of the substances and could be successfully removed by spectral subtraction. The most difficult aspect of the detection of these substances in latent fingerprints was visually locating the substance in the fingerprint in order to obtain a Raman spectrum.

Dermatoglyphics↗
PubMedDate not supplied

Effects of pyridinium chlorochromate adulterant (urine luck) on testing for drugs of abuse and a method for quantitative detection of chromium (VI) in urine.

Pyridinium chlorochromate (PCC) as an adulterant is popular for concealing drug-positive results. When 11-nor-delta9-THC-9-carboxylic acid (THC-acid) in urine was treated with 2 mmol/L of PCC (Cr6+ 104 microg/mL), 58-100% of the THC-acid was lost. The loss increased with decreasing pH and increasing reaction time (0-3 days). Free codeine and free morphine remained unaffected by PCC at pH within the physiological range of the urine (pH 5-7). At lower pH, the loss of free morphine varied from 0 to 100%. Amphetamine, methamphetamine, benzoylecgonine, and PCP remained unaffected by PCC when exposed to the oxidant for three days in urine pH of 3-7. Chromium (VI) from PCC in a urine solution was detected by a color reaction with 1,5-diphenylcarbazide (DPC). When the reagent was added to the urine, an immediate red-violet color appeared. The chromium-DPC complex showed a characteristic absorption peak at wavelength 544 nm with a shoulder at wavelength 575 nm. The ratio of absorption was used to identify the chromium compound. The concentration of chromium (VI) was determined by measuring absorption at wavelength 544 nm and was linear over 0.5-20 microg/mL. The limit of detection of the procedure was 0.37 microg/mL.

Anti-Infective Agents↗
PubMed2004

Club drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine.

Club drugs are substances commonly used at nightclubs, music festivals, raves, and dance parties to enhance social intimacy and sensory stimulation. The most widely used club drugs are 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy; gamma-hydroxybutyrate (GHB); flunitrazepam (Rohypnol); and ketamine (Ketalar). These drugs are popular because of their low cost and convenient distribution as small pills, powders, or liquids. Club drugs usually are taken orally and may be taken in combination with each other, with alcohol, or with other drugs. Club drugs often are adulterated or misrepresented. Any club drug overdose should therefore be suspected as polydrug use with the actual substance and dose unknown. Persons who have adverse reactions to these club drugs are likely to consult a family physician. Toxicologic screening generally is not available for club drugs. The primary management is supportive care, with symptomatic control of excess central nervous system stimulation or depression. There are no specific antidotes except for flunitrazepam, a benzodiazepine that responds to flumazenil. Special care must be taken for immediate control of hyperthermia, hypertension, rhabdomyolysis, and serotonin syndrome. Severe drug reactions can occur even with a small dose and may require critical care. Club drug over-dose usually resolves with full recovery within seven hours. Education of the patient and family is essential.

Anesthetics, Dissociative↗
PubMed1983

Legal implications of preparing and dispensing approved drugs for unlabeled indications.

The legal issues surrounding the potential liability of a pharmacist for dispensing or preparing drugs under conditions not contained in the FDA-approved labeling of a product are examined. Although the specific issue of liability of a pharmacist for preparing a drug in a nonapproved manner or dispensing a drug for a nonapproved use has not been adjudicated, based on evolving legal principles it appears that the pharmacist under certain circumstances may be held responsible for the drugs so prepared or dispensed. Preparation of a drug which is adulterated under the federal Food, Drug and Cosmetic Act appears to be negligent, although its precise effect will be dependent upon state law. Liability for dispensing for nonapproved uses will be minimized if the pharmacist, in the exercise of sound professional judgment, concludes that the use is rational, safe, and reasonable.

Drug Labeling↗
PubMed1976

Legal implications of preparing and dispensing drugs under conditions not in a product's official labeling.

The legal issues surrounding the potential liability of a pharmacist for dispensing or preparing drugs under conditions not contained in the official labeling of a product are examined. Although the specific issue of liability of a pharmacist for preparing a drug in a nonapproved manner or dispensing a drug for a nonapproved use has not been adjudicated, based on evolving legal principles it appears that the pharmacist will be held responsible for the drugs so prepared or dispensed. Preparation of a drug which is adulterated under the federal Food, Drug and Cosmetic Act appears to be negligent, although its precise effect will be dependent upon state law. Liability for dispensing for nonapproved uses may be minimized if the pharmacist, in the exercise of sound professional judgment, concludes that the use is rational, safe and reasonable.

Drug Compounding↗
PubMed1987

Rheumatic manifestations of diseases associated with substance abuse.

Rheumatic manifestations of substance abuse are uncommon but recognized complications. Repeated injections of drugs and adulterants represent repeated antigenic challenge. The population at greatest risk is that of young males, although females with eating disorders are more apt to develop myopathy, clubbing, or periostitis. Alcohol, the most common substance abused, is associated more often with myopathy. In IV drug abusers, hepatitis B viral infection, bacterial endocarditis, primary skeletal infections, and venous complications are most common in that order. However, the spectrum may evolve as the pattern of substance abuse changes. First, the frequency of cocaine dependence is rapidly approaching that of alcohol. Two regular cocaine users are reported as having Raynaud's phenomenon and abnormal serologies. Second, synthesis of lookalike drugs may produce new associations, such as parkinsonism after IV N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Third, the increased use of ipecac and purgatives in eating disorders is an important consideration in young women with otherwise unexplained myopathy or arthritis. Finally, patients with AIDS are presenting with autoimmune phenomena or a spectrum of unusual infections that change as the epidemic evolves. Increased recognition of these symptom complexes may lead to earlier, more accurate diagnoses and avoidance of unnecessary diagnostic evaluations and delays in treatment.

Alcoholism↗
PubMed1992

Pedagogical patronizing of the pharmacodynamic promises of illicit drugs.

A review of popular drug education textbooks and curricula indicated most juxtapose the physiologic effects of licitly manufactured drugs under headings representing illicitly prepared drugs. This misrepresentation ignores the literature, which is undivided, in reporting that illicit drugs contain adulterants and substitutes such as: sodium acetate, sodium cyclamate, dolomite, acetaminophen, gypsum, mannitol, inositol, lidocaine, amydricaine, benzocaine, caffeine, ephedrine, intercaine, phenylpropanolamine, piperocaine, procainamide, azopyridine, bromodiphenhydramine, ibuprofen, methaqualone, phenobarital trazodone, acetylcodine, codeine, quinine, quinidine, thallium, arsenic and strychnine. The temptation to extrapolate the results of licitly pure drug lots administered at precisely measured doses to represent the pharmacodynamics of illegally prepared drug lots administered at indiscernible doses must be avoided in drug educational resources. There is a pressing need to correct the factual base, both implied and suggestive, of drug education resources regarding the purity and toxicity of illicitly manufactured and purchased drugs.

Curriculum↗
PubMed1986

Osteolytic sinusitis and pneumomediastinum: deceptive otolaryngologic complications of cocaine abuse.

Recreational cocaine abuse via intranasal "snorting," "free-base" smoking, "body-packing," or intravenous injection can be lethal. Increasing illicit use of cocaine hydrochloride and the misuse of legal over-the-counter (OTC) nasal drugs are known causative agents of nasal septal perforation with loss of taste and smell. Although 2 to 3 mg/kg is the recommended maximum dose for topical anesthesia, cocaine snorters may use 1,000 mg or more daily on a "run." Furthermore, the newer route of smoking the extracted volatile "free-base" form of the adulterated street drug provides a plasma concentration producing the same physiological and subjective effects of intravenous cocaine. Presented are two cases exemplifying unusual complications of cocaine abuse: 1. total nasal septal bony and cartilaginous necrosis with resultant saddle-nose deformity and osteolytic sinusitis secondary to chronic intranasal "snorting" and 2. tracheobronchial rupture with pneumomediastinum secondary to smoking "free-base" cocaine.

Adult↗
PubMed2005

Proton nuclear magnetic resonance spectroscopy (NMR) methods for determining the purity of reference drug standards and illicit forensic drug seizures.

A rapid, sensitive, accurate, precise, reproducible, and versatile method for determining the purity of reference drug standards and the routine analysis of illicit drugs and adulterants using proton (1H) Nuclear Magnetic Resonance (NMR) Spectroscopy is presented. The methodology uses a weighed sample dissolved in a deuterated solvent or solvent mixture containing a high purity internal standard. The NMR experiment employs 8 scans using a 45 second delay and 90 degrees pulse. In the determination of purity of reference standards, the number of quantitative determinations available is equal to the number of peak groups that are baseline resolved. The relative standard deviation (RSD) of these signals is usually < 1% for pure standards, and the results agree well with other purity determining methods. This method can also aid in the determination of correct molecular weight for standards containing an unknown number of waters of hydration or an unknown number of acids per drug in salts. Because the molar response for the hydrogen nucleus is 1 for all compounds, and since no separation media are used, only one linearity study is required to test a probe. In the presented study, the linearity of the NMR probe was determined using methamphetamine HCl dissolved in deuterium oxide (D2O) with maleic acid as the internal standard (5 mg) for a range of concentrations from 0.033 to 69.18 mg/ml with a resulting correlation coefficient of >0.9999 for all 6 methamphetamine peak groups. The spectra of complex illicit heroin, methamphetamine, MDMA, and cocaine samples are presented, as well as an extensive list of compounds, their solubilities and the solvent(s) and internal standard used.

Journal Article↗
PubMed2001

Use of dynamically coated capillaries for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine using capillary electrophoresis.

A rapid, accurate, precise, reproducible, economical, and environmentally gentle method using capillary electrophoresis (CE) is presented for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine in seized drugs. The methodology uses a 32 cm by 50 microm capillary (length to detector 23.5 cm) with a commercially available buffer kit and diode array UV detection. Dynamic coating of the capillary surface is accomplished by flushing with base for 1 min, a proprietary polycation for 1 min, and then a proprietary polyanion for 2 min. This approach provides a relatively high and stable electroosmotic flow (EOF), even at low pHs. The background electrolyte (BGE) contains 75 mM phosphate buffer (pH 2.5) with the same polyanion as above. Using this methodology, amphetamine, methamphetamine, MDA, MDMA, MDEA, and an internal standard (n-butylamphetamine) are baseline resolved in less than 5 min. The run-to-run migration time %RSDs and peak area %RSDs are typically <0.3% and <2.1%, respectively. The day-to-day and capillary-to-capillary migration time %RSDs are <1.5% and <2.1%, respectively. The %RSDs of the relative migration times compared with the internal standard on a day-to-day and capillary-to-capillary basis are <0.2% and <0.06%, respectively. The linear dynamic range using peak areas range from 0.003 to 0.10 mg/mL. The correlation coefficients are >0.9998, with all calibration curves passing at or near the origin. Similar data are obtained for cocaine and its internal standard henyltoloxamine. None of the compounds usually encountered in illicit samples interfere with the target compound (e.g., methamphetamine and cocaine) or the internal standard. Quantitative results for synthetic mixtures and seized exhibits are in good agreement with actual values, and also with results obtained from other techniques. The relatively high EOF for the dynamically coated capillary system allows for the screening of basic, acidic, and neutral adulterants in drug seizures; identification is facilitated by the use of automated UV library searches.

Journal Article↗
PubMedDate not supplied

Solid-phase extraction of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid from urine drug-testing specimens with the cerex polycrom-THC column.

Confirmation of drugs of abuse by gas chromatography-mass spectrometry (GC-MS) is the most time-consuming process used by drug-testing laboratories. Cost effectiveness and competitive turnaround times for testing results demand fast, efficient, and reliable extraction methods. We applied the Cerex Polycrom-THC solid-phase extraction (SPE) column to the extraction of 11-nor-delta9-tetrahydrocannabinol carboxylic acid (9-THCA) from urine. This column uses an anion exchange divinyl-benzene copolymer, which requires no pH adjustment after hydrolysis of the THC-glucuronide with base, as is necessary with many other SPE columns. With urine, no preconditioning of the SPE column was necessary. After extraction, trimethylsilation derivatization was performed with N-methyl-N-(trimethylsilyl) trifluoroacetamide. This further improved efficiency because no heated incubation was required. A method correlation to an existing liquid-liquid extraction was performed. Analysis was on a Finnigan Voyager GC-MS with a 2.5-min run time per injection. Using 9-THCA-d9 deuterated internal standard, the assay was linear from 2 to 2000 ng/mL. Total precision at the 15-ng/mL cutoff concentration was 4.4%. The Cerex column was also evaluated for interference using two common drug-test adulterants, Klear and Urine Luck. Considerably less interference was observed when compared to an existing liquid-liquid method.

Cost-Benefit Analysis↗