INTERESTING INFORMATION

Equipment

Andor Labs would like to share some interesting information with those who would like to learn more about what goes on “behind the scenes” in our clinical laboratory as well as information regarding the drugs used to treat pain and those that are used illegally.

The Science behind Andor’s Testing

Andor Labs employs state-of-the-art LC-MS/MS (liquid chromatography-tandem mass spectrometry) instrumentation for all confirmation testing. LC-MS/MS is the most specific and sensitive technology available.

Andor tests for both parent drug and metabolite to provide information-rich results.

Sample preparation, specifically developed to address the chemical uniqueness of each drug class, removes potentially interfering substances prior to analysis.

Positive identification of each drug is confirmed using 3 to 7 drug-specific analytical parameters.

Each analysis is controlled with the use of 6 or 7 unique internal and externally-sourced quality control samples.

All analytical runs are reviewed independently by multiple experienced laboratory personnel.

LC-MS/MS chromatographic peaks used for quantitation and positive identification of Benzoylecgonine.

What is the difference between qualitative, semi-quantitative screening and quantitative drug confirmation?

HOW IS EACH TEST PERFORMED?

WHAT DO THE RESULTS MEAN?

IS VALIDITY TESTING IMPORTANT?

A Brief, Yet Comprehensive, Description

QUALITATIVE URINE DRUG SCREENING

Qualitative Urine Drug Screening is performed routinely at the collection facility using a commercial urine collection cup. Up to 12 drug classes can be assessed from a single collection, depending on the brand of collection cup employed. Qualitative Urine Drug Screening tests provide Positive/Negative (Yes/No) responses. Each testing panel on the collection cup is impregnated with (bio)chemical reagents that respond to the presence of drugs from a specific drug class. When there is a sufficient amount of drugs from the class present, the panel will change color to indicate the drugs are present. The specific drug or drugs that contribute to the positive response cannot be identified through Qualitative Urine Drug Screening. It should be understood that some drugs unrelated to the drug class being assessed with Qualitative Urine Drug Screening may lead to a false positive result. Alternatively, adulterants may mask the response of drugs that are present and lead to a false negative result.

Positive responses during Qualitative Urine Drug Screening provide a preliminary assessment of the types of drugs that may be present in the urine at the time of collection. To identify the drugs that caused the positive response or to determine if a specific drug is present at a concentration below the amount that triggers the response, Quantitative Urine Drug Confirmation Testing should be employed.

SEMI-QUANTITATIVE URINE DRUG SCREENING

Semi-Quantitative Urine Drug Screening is an alternative to Qualitative Urine Drug Screening. Semi-Quantitative Urine Drug Screening is performed using an auto-analyzer typically found in clinic, hospital and toxicology laboratories. Again, a wide variety of drug classes can be assessed from a single collection, depending on how the auto-analyzer is programmed. Semi-Quantitative Urine Drug Screening tests provide numerical results related to the summed concentrations of drugs within a specific class that are present in the sample. As with Qualitative Urine Drug Screening, Semi-Quantitative Screening utilizes (bio)chemical reagents that respond to the presence of drugs from a specific class. However, for Semi-Quantitative Screening, the response generated is based on instrument calibration. Calibration is the relationship between responses generated by a compound representative of the drug class at different concentrations (i.e., concentration-response). The numerical result represents the summed concentrations from all drugs in the class that contribute to the response. For instance, the numerical result generated by the Semi-Quantitative Screening test for Opiates includes the summed contributions from Morphine, Codeine, Hydrocodone, Hydromorphone, and to a lesser extent, Oxycodone and Oxymorphone. The specific drug or drugs that contribute to the positive response cannot be identified through Semi-Quantitative Urine Drug Screening.

Importantly, not all forms of a drug elicit a response and not all drugs lead to the same response. Drugs may be present in urine as the original drug compound or as drug metabolites; metabolites are chemically related to the original drug compound but may or may not lead to an instrument response. For instance, benzodiazepine drugs are found in urine primarily as drug-glucuronide metabolites of the original drug compound: drug-glucuronide metabolites do not trigger a response. Thus, although there may be a high concentration of benzodiazepine drug-glucuronide present the urine, the concentration of the original drug compound is insufficient to trigger a response.

A numerical response during Semi-Quantitative Urine Drug Screening provides a preliminary assessment of the type and concentration of drugs that may be present in the urine at the time of collection. To identify the drugs that caused the numerical response or to determine if a specific drug is present at a concentration below the amount that triggers the response, Quantitative Urine Drug Confirmation Testing should be employed. As with Qualitative Urine Drug Screening, some drugs unrelated to the drug class being assessed may lead to a false response and adulterants can mask the response of drugs that are present yielding a false negative result.

QUANTITATIVE URINE DRUG CONFIRMATION TESTING

Quantitative Urine Drug Confirmation Testing provides definitive proof of the presence and concentration of specific drugs in a urine collection. It is used to define further the results of Qualitative or Semi-Quantitative Urine Drug Screening. Quantitative Urine Drug Confirmation Testing is typically performed using gas chromatography (GC) or, in recent years, liquid chromatography (LC) to separate the drugs within a urine sample prior to detection using mass spectrometry (MS). GC/MS and LC/MS instrument systems are found in hospital and toxicology laboratories and must be operated by skilled personnel.

GC/MS and LC/MS instruments are sensitive; that is, they can detect drugs present at concentrations far below the cutoff values for Qualitative and Semi-Quantitative Drug Screening. GC/MS and LC/MS instruments are specific; that is, they can identify individual drugs and drug metabolites present in a sample containing multiple drugs. For instance, drugs commonly included in an Opiate panel are Morphine, Codeine, Hydrocodone, Hydromorphone, Oxycodone and Oxymorphone. The presence/absence of each drug in the class can be confirmed as well as the concentration of each determined simultaneously.

Positive identification is made by the order the drugs enter the mass spectrometer from the liquid chromatographic system and by the mass (e.g., molecular weight) detected by the mass spectrometer in relation to the order and mass of a known amount of a related compound (i.e., internal standard). Similar to Semi-Quantitative Screening, a concentration-response calibration must be performed for each drug to be quantified accurately. Only drugs that are calibrated will be identified and quantified; other drugs within the class that are present but are not calibrated will not be detected. For instance, if Benzoylecgonine (the major metabolite of Cocaine) but not Cocaethylene (a Cocaine metabolite produced only when the patient has consumed alcohol in addition to Cocaine) is calibrated, only Benzoylecgonine will be identified and quantified. Even though Cocaethylene may be present, it will not be detected.

Importantly, a urine specimen can be pretreated prior to MS detection to remove substances that can interfere with detection and/or to convert drug metabolites to the original drug form. This provides for increased specificity and sensitivity and, thus, more confidence in results.

URINE VALIDITY TESTING, AN IMPORTANT ADJUNCT TO URINE DRUG SCREENING AND TESTING

Urine Validity Testing is performed to determine if the urine specimen is consistent with human urine or has been altered. Urine Validity Testing includes determinations of urine pH (a measure of acidity/alkalinity), specific gravity (a measure of the amount of salts and other dissolved compounds), creatinine (a measure of muscle breakdown that is related to kidney function), nitrites (potassium nitrite or sodium nitrite added to a urine specimen to foil a drug test) and oxidants (bleach, hydrogen peroxide or other oxidizing agent added to foil a urine test).

Estimate of pH, creatinine and oxidant can be obtained via urine collection cups with these test panels. More accurate measures are obtained using an auto-analyzer (see description under Semi-Quantitative Urine Drug Screening). If a urine specimen is determined to be invalid*, no further screening or testing should be performed, as those results may be invalid.

* Invalid means pH, specific gravity and/or creatinine values fall outside of the physiological range, and/or a nitrite or oxidant is present.

The Dilemma of the Pain Management Physician and the Role of the Clinical Laboratory

Pain management physicians walk a thin line between caring for patients with debilitating pain and dismissing clients who abuse the doctor-patient relationship.

It is unfortunate that the physician must spend valuable time that should be devoted to improving the lives of those truly suffering in pain with those who come to the physician to support a drug addiction or those who seek profit in dealing prescription medications.

Pain management physicians rely on many resources to help distinguish the legitimate from the illegitimate patient, including serial assessment of bodily fluids for the presence of prescribed and non-prescribed medications and illicit drugs.

It is the responsibility of the clinical laboratory to concentrate on providing useful information on time and in a format that allows for fast and effective interpretation. Thus the clinical laboratory should apply current scientific technology and forward thinking methodologies to best guide the physician in making appropriate treatment decisions.

Drugs analyzed by Andor Labs by class, their trade names and metabolites

indicates quantified directly

indicates quantified by virtue of hydrolysis of conjugate to free drug

OPIATES

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Codeine Tylenol+Codeine Codeine-glucuronide, Hydrocodone, Morphine, Norcodeine, Normorphine
Morphine Avinza, Kadian, Kapanol, MS Contin, MSIR Codeine,Normorphine, Dihydromorphinone, Hydromorphone, Morphine-glucuronide(s)

OPIOIDS

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Buprenorphine Buprenex, Suboxone, Subutex Buprenorphine-glucuronide, Norbuprenorphine, Norbuprenorphine-glucuronide
Fentanyl Actiq, Duragesic, Fentora, Sublimaze Norfentanyl, piperidine analogues
Hydrocodone Hydrocet, Lorcet, Lortab, Norco, Vicodin Acetylhydrocodone, Dihydrocodeine , Hydrocodol(s), Hydrocodone-glucuronide , Hydromorphol(s), Hydromorphone, Norhydrocodone, Norhydromorphone, Normorphine
Hydromorphone Dilaudid, Hydrostat Dihydroisomorphine, Dihydroisomorphine-glucoside, Dihydroisomorphine-glucuronide, Dihydromorphine, Hydromorphone-glucoside, Hydromorphone-glucuronide, Norhydromorphone
Meperidine Demerol Hydroxymeperidine(s), Hydroxymethoxymeperidine, Hydroxynormeperidine, Meperidine-oxide, Normeperidine, Norpethidinic acid, Pethidinic acid
Methadone Dolophine, Methadose Ethylidine-dimethyl-diphenylpyrrolidine (EDDP) , EDDP-glucuronide, EDMP, EDMP-glucuronide, Methadol, Methadone-glucuronide, Normethadol
Oxycodone Endocet, Oxycontin, Percocet, Roxicodone, Roxicet Noroxycodone, Noroxycodol(s), Noroxymorphone, Oxycodol(s), Oxycodone-“conjugate”, Oxymorphol, Oxymorphone, Oxymorphone-glucuronide
Oxymorphone Opana Hydroxyoxymorphone, Noroxymorphone , Oxymorphol, Oxymorphone-glucuronide
Propoxyphene Darvocet, Darvon Norproxyphene
Tapentadol* Nucynta Desmethyltapentadol, Tapentadol-glucuronide, Tapentadol-sulfate
Tramadol Ryzolt, Tramal, Ultram Desmethyltramadol(s) , Desmethyltramadol-glucuronide
* Technically Tapentadol is not an opioid, it is listed here as a convenience

MUSCLE RELAXANTS

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Carisoprodol Carisoma, Soma Hydroxycarisoprodol, Hydroxycarisoprodol-“conjugate”, Hydroxymeprobamate, Hydroxymeprobamate-“conjugate”, Meprobamate
Meprobamate Miltown Hydroxymeprobamate

BENZODIAZEPINES

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Alprazolam Xanax Alprazolam-glucuronide, Dihydroxyalprozolam , HMTBP, Hydroxyalprazolam(s), Hydroxyalprazolam-“conjugate”
Clonazepam Klonopin Aminoclonazepam
Diazepam Diastat, Valium Hydroxynordiazepam, Nordiazepam, Nodiazepam-glucuronide, Oxazepam, Temazepam
Flunitrazepam Rohypnol Aminoflunitrazepam
Lorazepam Ativan Lorazepam-glucuronide
Oxazepam Alepam, Medopam Oxazepam-glucuronide
Temazepam Desmethyltemazepam, Desmethyltemazepam-glucuronide, Temazepam-glucuronide, Oxazepam

AMPHETAMINES

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Amphetamine Adderall, Benzedrine, Dexedrine, Vyvanase Benzoic acid, Hippuric acid, Hydroxyamphetamine, Norephedrine, Phenylpropanone

BARBITURATES

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Amobarbital Amytal Sodium Glucopyranosylamobarbital, Hydroxyamobarbital
Butalbital Dolgic, Dolgic Plus, Fioricet, Fortabs Butalbital-“conjugate”, Isobutyldihydroxypropylbarbituric acid, Urea
Pentobarbital Nembutal Ethylhydroxymethylbarbituric acid, Hydroxypentobarbital
Phenobarbital Donnatal, Luminal Phenobarbital-glucoside, Phenobarbital-glucuronide
Secobarbital Seconal, Tuinal Hydroxysecobarbital, Hydroxysecobarbital-glucuronide

ILLICITS

Drug Name Trade Names (listed alphabetically) Metabolites (listed alphabetically)
Cocaine Benzoylecgonine (BZE), Cocaethylene, Ecgonine, Ecgoninemethylester (EME), Norcocaine
Ethanol Ethyl-glucuronide, Ethyl-sulfate
Heroin (Diacetylmorphine) Monoacetylmorphine (6-MAM)
Methamphetamine Amphetamine, Hydroxymethamphetamine
Methylenedioxyamphetamine (MDA) Dihydroxyamphetamine, Hydroxymethoxyamphetamine
Methylenedioxyethylamphetamine (MDEA) Dihydroxyethylamine (DHEA), MDA
Methylenedioxymethamphetamine (MDMA) Dihydroxymethamphetamine (HHMA), Hydroxymethoxyamphetamine (HMA), Hydroxymethoxymethamphetamine (HMMA), HMMA-glucuronide, HMMA-sulfate, MDA, MDA-glucuronide, MDA-sulfate
Phencyclidine Phencyclidine-glucuronide, Phenylpiperdinocyclohexanol-glucuronide, Phenylcyclehexaylhydroxypiperdine-glucuronide
Cannabis (Tetrahydrocannabinol, THC) Hydroxy-THC, Nor-carboxy-THC (THCA), Nor-carboxy-THC-glucuronide(s)

Drugs with Amphetamine as a Metabolite

Amfetaminil (Aponeuron)
Ethylamphetamine (Apentinil, Adiparthrol)
Clobenzorex (Asenlix, Dinintel, Finedal, Rexigan)
Fenproporex (Perhoxene)
Mefenorex (Anexate, Pondinil, Rondimen)
Prenylamine (Segontin)
Selegiline (Eldepryl)

Drugs with Methamphetamine as a Metabolite

Benzphetamine (Didrex)
Dimethylamphetamine (Metrotonin)
Fencamine (Altimine, sicoclor)
Furfenorex (Frugalan)
Selegiline (Eldepryl)


Opiate/Opioid Metabolism Pathways Chart

METABOLISM OF OPIATES/OPIOIDS

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Benzodiazepines Metabolism Pathways Chart

METABOLISM OF BENZODIAZEPINES

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