Cocaine

Because cocaine is weakly basic and oral fluid is generally more acidic than plasma, the concentration of ionized cocaine in oral fluid is generally higher than plasma and is detectable for longer time periods as compared to plasma. When cocaine is consumed by smoking or through intranasal routes, oral fluid plasma ratio is higher for several hours. There are a number of reports on excretion of cocaine and its metabolites in oral fluid. Cocaine and its metabolites (anhydroecgonine,...

Passive Exposure to Cocaine Smoke

Passive inhalation of cocaine smoke leading to a positive test for benzoylecgonine in adults has not been reported in the literature. Passive exposure to cocaine smoke can result in absorption of cocaine and excretion of a detectable amount of benzoylecgonine into the urine (16). In this study, all urine specimens collected from six individuals following passive exposure to 100 or 200 mg of vaporized cocaine tested negative for benzoylecgonine using the standard 300 ng ml cutoff. Peak...

Nontricyclic antidepressants

After discovery of TCAs and monoamine oxidase inhibitors, collectively called first-generation antidepressants, many other classes of antidepressants were discovered. These include amoxapine and maprotiline that affect reuptake of monoamines similar to secondary amine TCAs. Trazodone is a weak inhibitor of serotonin reuptake but has little effect on norepinephrine uptake. Bupropion inhibits reuptake of norepinephrine and dopamine. In addition to its use as an antidepressant, bupropion is used...

Cannabinoids

11-nor-delta 9-tetrahydrocannabinoid (THC) is the principle psychoactive cannabinoid in marijuana. Its major urinary metabolites are 11-nor-delta 9-tetrahydrocannabinoid carboxylic acid (THCA) and its glucuronide conjugate. Cannabinoid metabolites immunoassays (EMIT, FPIA, CEDIA, and KIMS) are designed for THCA detection and are calibrated with this compound typical cutoffs used are 20, 25, 50, and 100ng ml of THCA. These assays do have substantial cross-reactivity with other cannabinoids, and...

References

Spectrophotometric detection of iodide and chromic (III) in urine after oxidation to iodine and chromate. J Anal Toxicol 2005 29 658-663. 2. Burrows DL, Nicolaides A, Rice PJ, Duforc M, et al. Papain a novel urine adulterant. J Anal Toxicol 2005 29 275-295. 3. George S, Braithwaite RA. An investigation into the extent of possible dilution of specimens received for urinary drugs of abuse screening. Addiction 1995 90 967-970. 4. Needleman SD, Porvaznik M. Creatinine analysis in...

Smoking and Serum Drug Concentrations

Approximately 4800 compounds are found in tobacco smoke including nicotine and carcinogenic compound, for example polycyclic aromatic hydrocarbons (PAHs) and N-nitroso amines. Compounds in tobacco smoke can induce certain cytochrome P450 enzymes responsible for metabolism of many drugs. PAHs induce CYP1A1, CYP1A2, and possibly CYP2E1. Smoking may also induce other drug metabolism pathways such as conjugation (65). Cigarette smoke is responsible for pharmacokinetic drug interactions, not...

Therapeutic Drug Monitoring of Antiasthmatic Drugs

Theophylline is a bronchodilator and respiratory stimulant effective in the treatment of acute and chronic asthma. The drug is readily absorbed after oral absorption, but peak concentration may be observed much later with sustained release tablets. The bronchodilator effect of theophylline is proportional to the log of serum drug concentration over a range of 5-20 g mL (129). Adverse reactions may be observed Therapeutic Drug Monitoring of Cardioactive Drugs Therapeutic Drug Monitoring of...

Amitava Dasgupta PhD

Therapeutic Drug Monitoring of Digoxin 2. Discovery of Endogenous DLIS 3. Positive and Negative Interference of DLIS in Serum Digoxin Measurement Impact on TDM of Digoxin 4. Is DLIS a Natriuretic Hormone 5. Effect of Fab Fragment of Antidigoxin Antibody on Digoxin Immunoassays 6. Interference of Spironolactone, Potassium Canrenoate, and Canrenone in Digoxin Assays 7. Interference of Complementary and Alternative Medicines in Digoxin Measurement Digoxin is a cardioactive drug with a narrow...

Diluted Urine

A negative result for the presence of abused drugs in a urine specimen does not mean that no drug is present. It is possible that the amount of drug is below the cut-off values for detection in the laboratory assays. Diluting urine is a simple way to make an otherwise positive drug tests negative if the original concentrations of drugs in the urine are slightly above the cut-off values. Federal guidelines recommend placing a toilet bluing agent in the toilet tank if possible so that the...

Mechanism Of Action Of Adulterants

Adulterants such as bleach cause a false-positive result in THC radioimmunoassay but false-negative results with both FPIA and EMIT assay. These erroneous results are due to direct effect of bleach on the reagents in the immunoassays (13,43). Adulterants that are strong oxidizing agents such as Klear (potassium nitrite), Urine Luck (PCC) and Stealth (peroxidase and hydrogen peroxide) cause false-negative results in the immunoassays used for screening drugs by directly destroying THC metabolites...

Pharmacokinetics and Serum Drug Concentrations

When a drug is given orally, it undergoes several steps in the body and its concentration in serum or whole blood is affected by certain steps. 1. Liberation The release of a drug from the dosage form (tablet, capsule, extended release formulation) 2. Absorption Movement of drug from site of administration (for drugs taken orally) to blood circulation 3. Distribution Movement of a drug from the blood circulation to tissues. This distribution in most cases is reversible. Certain drugs also cross...

Analytical Considerations

Equilibrium dialysis technique was used by several investigators to estimate free lidocaine concentration. Routledge et al. subjected two 1 ml aliquots of plasma to equilibrium dialysis using a Teflon equilibrium dialysis cell. The dialysis was performed against Sorenson's phosphate buffer (containing 0.5 w v sodium chloride), and the pH was adjusted to 7.4 to which lidocaine hydrochloride was added (3 g mL buffer). This concentration was achieved by adding unlabeled lidocaine hydrochloride...

Drug metabolism and clearance in neonates children and elderly

In the fetus, CYP3A7 is the major hepatic cytochrome responsible for steroid metabolism. Variably expressed in the fetus, CYP3A5 is also present in significant level in half of the children. However, in adults, CYP3A4 is the major functional hepatic enzyme responsible for metabolism of many drugs. CYP1A1 is also present during organogenesis whereas CYP2E1 may be present in some second trimester fetuses. After birth, hepatic CYP2D6, CYP2C8 9, and CYP2C18 19 are activated. CYP1A2 becomes active...

Siberian Ginseng Asian Ginseng and Ashwagandha

There is one case report of interference of Siberian ginseng in serum digoxin measurement. A 74-year-old man had a steady serum digoxin level of 0.9-2.2 ng mL for 10 years. His serum digoxin increased to 5.2 ng mL on one occasion after taking Siberian ginseng. Although the level was toxic, the patient did not experience any sign or symptoms of digoxin toxicity. The patient stopped taking Siberian ginseng, and his digoxin level returned to normal (106). However, in our experience, Siberian...

Alcohol and Drug Interactions

Fatal toxicity may occur from alcohol and drug overdoses. In many instances, in the presence of alcohol, a lower concentration of drug may cause fatality because of drug-alcohol interactions. In a Finnish study, it was found that median amitriptyline and propoxyphene concentrations were lower in alcohol-related fatal cases compared with cases where no alcohol was involved. The authors concluded that when alcohol is present, a relatively small overdose of a drug may cause fatality (56). Although...

Therapeutic Drug Monitoring of Antidepressants

TCAs, including amitriptyline, doxepin, nortriptyline, imipramine, desipramine, protriptyline, trimipramine, and clomipramine were introduced in the 1950s and the 1960s. These drugs have a narrow therapeutic window, and therapeutic drug monitoring is essential for efficacy of these drugs as well as to avoid drug toxicity. Issues in therapeutic drug monitoring of these drugs are discussed in Chapter 8. The efficacy of lithium in acute mania and for prophylaxis against recurrent episode of mania...

Tai C Kwong PhD

Analytical True Positive Versus Clinical False Positive 3. Clinical False-Positive Results A confirmed positive drug test reassures all the parties involved in the drug testing process that the reported positive result is an analytical true positive and as such is evidence that the individual has been exposed to the drug. That individual may not be a drug abuser and may have a valid alternative explanation for the positive result. In this context, an analytical true positive result may be a...

Oleander poisoning and Oleander Containing Herbs

The oleanders are evergreen ornamental shrubs with various colors of flowers that belong to the Dogbane family and grow in the Southern parts of the USA from Florida to California, Australia, India, Sri Lanka, China, and other parts of the world. All parts of the oleander plant are toxic. Human exposure to oleander includes accidental exposure, ingestion by children, administration in food or drink, medicinal preparations from oleander (herbal products), and criminal poisoning (90-93). Despite...

How To Detect And Remove Antibody Interference

If a test result is unexpected and heterophilic antibody is suspected as the source of interference, several strategies can be adopted for investigation. 1. Dilution linearity study with the specimen is the simplest way to document interference when observed values after dilution deviate significantly from the target values. Figure 1 illustrates the effect of successive dilutions of a HAMA containing sample (spiked with 32 g mL of theophylline but observed value was 59 g mL) compared to a...

Products Claiming to Beat Hair Drug Test

There are numerous sites on the Internet that sell products and claim to beat or pass the hair drug test. Searching on Google using the phrase pass hair drug test showed 6,620,000 hits in 0.22 s. Although most of these sites claim that their product works 100 , and some with money back guarantee, there is very little scientific evidence whether these products actually work. Rohrich et al. (54) investigated the effect of shampoo Ultra Clean (Zydot Unlimited, Tulsa, Ok) on eliminating THC,...

Common Household Chemicals as Urinary Adulterants

People try to beat drug testing by adding adulterants into urine specimens. Several adulterants can cause false-negative results in drug testing by immunoassays. Common adulterants for masking drug testing are as follows and detection of these adulterants by specimen integrity tests is given in Table 2. 5. Golden Seal tea (produces dark urine). AlthoughFPIA is less subjected to interference from adulterants compared to the EMIT, some interference has also been reported with FPIA. Sodium...

Methods for determination of nontcas

There is no reliable spot test for commonly used non-TCAs. Also, currently there are no widely used immunoassays for non-TCAs. Chromatography techniques are most common, and well-established techniques are available for measurements as either a single drug or a group. Most of these antidepressants are well detected during comprehensive drug screening performed by using GC or HPLC. Like TCAs, GC is widely used for screening and quantitation of non-TCAs. The methods involve either liquid-liquid...

Extemporaneous Preparations Containing Cocaine

There are no prescription medications that contain cocaine. Extemporaneous preparations containing cocaine, however, are used as local anesthetics in ENT surgery and in ophthalmological procedures. Patients who had had these ENT and ophthalmo-logical procedures tested positive for benzoylecgonine up to 2-3 days following the procedure (9,10). TAC (tetracaine, adrenalin, and cocaine) is a topical preparation used for surface anesthesia during various surgical procedures. It was used extensively...

Urine Specimens

Common household chemicals such as laundry bleach, table salt, toilet bowl cleaner, hand soap and vinegar have been for many years used as adulterants of urine specimens in an attempt to avoid a positive drug test. There is also a popular belief that drinking Golden Seal tea helps to escape detection of an abused drug. More recently, a variety of products have become commercially available which can be ordered through Internet sites (http www.bdtzone.com, http pass-drug-test.com and so on) and...

Issues of Special Interest in Oral Fluid Testing

Although oral fluid can be collected under direct supervision and opportunity for sample adulteration is low, measurement of human IgG is recommended for sample validity. 2. To avoid adulteration, supervision of donor for 10-20 min is recommended prior to sampling. The donor should not put anything in his her mouth during this period. 3. To ensure that positive THC result, using point of care testing device, on an oral fluid specimen is from active exposure, SAMHSA proposes collection of a...

Substances Known to Metabolize to Methamphetamine and Amphetamine

Many medications and substances are known to metabolize to methamphetamine or amphetamine, thus giving analytical true positives (Table 2). If a patient is on one of these medications, the positive result is a clinical false positive. Enantiomeric analysis may be useful in verifying that the positive result was due to the use of a prescription drug. For example, selegiline, a drug used in the treatment of Parkinson's Examples of Amphetamines-Containing products3 Substances known to contain...

False Positive Methamphetamine

In 1993, Hornbeck et al. (44) demonstrated that methamphetamine can be generated from high levels of pseudoephedrine or ephedrine in injection ports at a temperature of 300 C after derivatization with 4-CB, HFBA, and TPC. They investigated the effect of changing conditions and concluded that the most important conditions for this thermal conversion are the high injector temperature and high concentrations of pseudoephedrine or ephedrine. In their experiments, the highest amphetamine...

Detection of Specific Drugs in Meconium

Although meconium is more easily collectable from a newborn as compared to urine, its analysis is considerably more difficult. Before analysis, it is important that the sample be homogenized, as meconium is a non-homogenous and is a gelatinous material. The methods of analysis include immunoassays for screening and GC-MS for confirmation. Although there is no FDA-approved immunoassay for drugs of abuse testing for meconium, the laboratories generally modify commercially available urine assays...

Prescription Medications Containing Amphetamine or Methamphetamine

Drug Enforcement Agency listed amphetamine and methamphetamine as Schedule II controlled substances. Clinical uses include treatment of attention deficit disorder with hyperactivity, narcolepsy, and obesity. Pharmaceutical methamphetamine is d-methamphetamine. Amphetamine, however, is available as d-amphetamine as well as a mixture of d- and -isomers. Medications containing d-amphetamine Dexedrine , Destrostat , racemic amphetamine Adderall , and d-methamphetamine Deoxsyn are listed in Table 2....

Juice and Cranberry Juice

Pomelo, closely related to grapefruit, interacts with cyclosporine. In a study involving 12 healthy male volunteers, 200 mg dose of cyclosporine was administered with 240 ml of pomelo juice. The average maximum concentration of cyclosporine in blood was 1494 ng mL when cyclosporine was administered with pomelo juice compared to an average concentration of 1311 ng mL when cyclosporine was administered along with water. However, intake of cyclosporine along with cranberry juice had no effect on...

Interference of spironolactone potassium canrenoate and canrenone in digoxin assays

Spironolactone, a competitive aldosterone antagonist, has been used clinically in the therapy of hypertension and congestive heart failure for a long time. Spironolactone is rapidly and extensively metabolized, and its metabolite canrenone is also pharmacologically active. Spironolactone and canrenone have structural similarity with digoxin Fig. 1 . Although not in formulary in the USA, potassium canrenoate is used in Europe and other countries. Potassium canrenoate is also metabolized to...

Application of gc gcms hplc and hplcms for drug analysis

Although immunoassays are widely used for routine TDM in clinical laboratories, other analytical techniques such as GC, HPLC, GC MS, and HPLC MS are also used for determination of concentrations of various drugs in clinical laboratories Table 2 . These alternative techniques, especially GC MS and HPLC MS, are very sensitive and specific for a chosen analyte whereas immunoassays suffer from multiple problems including interferences from compounds with similar structures, hook effect, and...

Bilirubin

Bilirubin is derived from hemoglobin of aged or damaged red blood cells RBC . Bilirubin does not have iron and is rather a derivative of the heme group. Some part of serum bilirubin is conjugated as glucuronides direct bilirubin the unconjugated bilirubin is also referred as indirect bilirubin. In normal adults, bilirubin concentrations in serum are from 0.3 to 1.2 mg dL total and lt 0.2 mg dL conjugated 5 . In different forms of jaundice, total bilirubin may increase to as high as 20 mg dL,...

Drug Interactions with Piperine Major Constituent of Black Pepper

Piperine, a major constituent of black and long pepper, has been reported to act as bioavailability enhancer of several drugs by inhibiting drug metabolism and by increasing oral absorption. Bharadwaj et al. reported that piperine inhibits both the drug transported P-glycoprotein and the major drug metabolizing enzyme CYP3A4. Therefore, dietary piperine could affect plasma concentrations of drugs that are substrates of P-glycoprotein or CYP3A4 enzyme especially if administered orally 138 ....

Pharmacokinetics and Metabolism of TCAs

Most of TCAs are well absorbed and reach peak plasma concentrations within 2-12 h. Owing to their lipophilic properties, they have a very large volume of distribution. Many of TCAs are tertiary amines and are metabolized by the cytochrome P450 isoenzyme system to secondary amines, which are also active. Some TCAs are metabolized to hydroxylated metabolites that may also be active and are further metabolized by glucuronidation. Some pharmacokinetics properties of TCAs are summarized in Table 1....