Affectors of Laboratory Results: Part VII

This week, let�s look at a compiled list of individual sources of potential errors in a laboratory analysis that can affect (increase or decrease in analyte concentration) reported results.

Sources of error that can result in a DECREASE in reported drug concentration:
Adsorption, Non-specific (sticking of drug to laboratory glassware, etc.)
Analyte-Matrix Interaction (the drug interacts with a part of the dosage form)
Calculations Incorrect (dilution factors, etc.)
Chemical Contamination (may interfere with the analytical method)
Chemical Hydrolysis (degradation of the drug)
Chemical Reactivity (resulting in a new chemical entity/entities being formed)
Degassing of Solutions (results in less sample being pipetted)
Denaturation (can result in entrapment and loss of the drug)
Entrapment, Physical (leading to incomplete extraction, improper solvent selection)
Evaporation (if analyte is volatile)
Improper standards used (salt form, ester form, hydration state)
Incomplete Derivatization (sometimes used for chromatographic/spectrometric methods)
Incomplete Extraction (from improper sample preparation)
Incomplete Precipitation (during sample preparation)
Ionic Strength (can result in precipitation of the drug)
Mechanical Shearing (polymers)
Microbial Contamination (may modify the drug)
Particulates (possible loss of drug or if drug adsorbs to a particulate material)
pH (degradation of the drug)
Photolysis (degradation of a light-sensitive drug)
Thermal Degradation (loss of thermolabile drug if exposed to heat)

Sources of error that can result in an INCREASE in reported drug concentration:
Calculations Incorrect (dilution factors, etc.)
Chemical Reactivity (may produce a chemical with stronger chromophores)
Evaporation (loss of the solvent)
Improper standards used (salt form, ester form, hydration state)
Microbial Contamination (may add additional entities/byproducts to the sample)
pH (may alter absorptivity of analyte)

Laboratory Procedures that can alter laboratory results:
Calculations
Degassing
Extraction
Heating at improper temperatures
Light exposure
Mixing (foaming)
pH adjustment
Pipetting
Precipitation steps
Storage conditions
Vortexing (foaming)
Others

Laboratories must follow established standard operating procedures to ensure their clients of valid results. They must also use quality reference standards and chemicals of appropriate quality and grade (HPLC grade, Spectroscopic grade, etc.) Incidentally, these grades are higher purity grades than USP grades. Laboratories must also have appropriate and well-maintained and calibrated analytical instruments operated by qualified personnel. The selection of the laboratory to be used by a compounding pharmacy is a critical decision.

Next week, we will conclude this series on laboratory results by presenting a table of different analytical methods that can be used for different compounded dosage forms. Then, we will pick up on other topics the following week.

Loyd V. Allen, Jr., Ph.D., R.Ph
Editor-in-Chief

The following citations represent a sampling of abstracts added to the CT.com literature search database featuring andropause and testosterone replacement/testing in men.

• Cutter CB. Compounded percutaneous testosterone gel: use and effects in hypogonadal men. J Am Board Fam Pract 2001; 14(1): 22-32.
• Elin RJ, Winters SJ. Current controversies in testosterone testing: Aging and obesity. Clin Lab Med 2004; 24(1): 119-139.
• Gooren LJ, Bunck MC. Androgen replacement therapy: Present and future. Drugs 2004; 64(17): 1861-1891.
• Mohr BA, Guay AT, O�Donnell AB et al. , bound and nonbound testosterone levels in normally ageing men: Results from the Massachusetts Male Ageing Study. Clin Endocrinol 2005; 62(1): 64-73.
• Rhoden EL, Morgenthaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004; 350(5): 482-492.

This week on the International Journal of Pharmaceutical Compounder�s complimentary listserv participants discussed:

• A pharmacist in Georgia had a patient bring in Posterisan (a product for hemorrhoids) from Germany. He asked if someone from Germany could help him with the ingredients. A pharmacist from Brussels, Belgium answered with the ingredients.
• A pharmacist in Canada asked for a formula for PHMB (polyhexamethylene biguanide) eyedrops 0.02% and a pharmacist in the USA answered with the information.
• A pharmacist just getting started in compounding asked for help on how to fill syringes with a BHRT topical preparation and get all of the air out. There have been more than 10 responses with tips on how to accomplish this.

The Pharmaceutical Press has alerted us that during the final stages of production of the 34^th edition of Martindale a one page section of the index between `Bronchorinol' and `Bug Proof' (page 2487, second column from left, a little more than halfway down the column) was inadvertently omitted. This file may also be obtained from the Pharmaceutical Press website: www.pharmpress.com.

Additional questions may be sent to pharmpress@ameritech.net

Now you can obtain Endotoxin Levels with one click. From the CT.com website click on �Compounding Tools� and �Endotoxin Tool�, then choose the first letter of the drug and then the drug of interest from the menu of drugs provided. You will given the maximum allowed bacterial endotoxin unit levels in sterile preparations.

What�s important about Endotoxins? They are a subset of pyrogens that come from gram negative bacteria.

Endotoxins are potent, toxic, very stable and present in many pharmaceutical ingredients and on surfaces that come into contact with the product when formulated for parenteral administration. They are water soluble, will pass through 0.2 �m filters, are not destroyed by autoclaving and are insoluble in organic solvents. Endotoxins are very difficult to eliminate in a final preparation; thus, procedures are generally directed at eliminating endotoxins during the preparation process.

Upon inadvertent administration of endotoxins to humans, a number of events may occur, ranging from fever through a cascade of pathogenic responses and even death.

There is an acceptable endotoxin load that the body can generally tolerate without experiencing the associated adverse events. This generally accepted endotoxin limit (EL) is defined as:

EL = K/M, where K is the threshold human pyrogenic dose of endotoxin per kg of body weight per hour, which is 5.0 EU/kg for parenteral drugs (except those administered intrathecally) and 0.2 EU/kg for the intrathecal route of administration, and where M is the maximum recommended human dose/kg of body weight that would be administered in a single one hour period.

Isolator for Automated Fillers

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Flow Sciences Hires Boutique Advertising Agency

Flow Sciences, Inc. of Leland, NC has joined up with Triovisions, a creative productions and marketing firm, headquartered in Wilmington, NC.� Triovisions will work with Flow Sciences, Inc, an established leader in containment solutions for all sizes and applications, to enhance the company�s corporate identity and position the company for future growth.

Flow Sciences, Inc plans to launch several new products this year, continuing the rapid expansion of its product lines of containment solutions from benchtop laboratory solutions through robotic and automated equipment enclosures to large-scale production facilities containment products.

�The demand for our engineering expertise in the safe containment of chemical and compound processing has been tremendous, and we are at a point where we need to move to the next level through strategic marketing and tactical execution,� stated Ray Ryan, Founder and CEO, Flow Sciences, Inc.

Flow Sciences, Inc. (FSI) designs and manufactures containment solutions for Research and Development Laboratories, Pilot Plants and Laboratory Automation Equipment and Robotics where toxic or noxious potent powders, fluids or gases require safe handling while weighing, mixing or manufacturing.�

For more information please visit www.flowsciences.com or call Steve Janz at 910.763.1717