Affectors of Laboratory Results: Part III

Part I of this weekly series introduced the area of potential errors that may result in pharmaceutical compounding and laboratory testing. It introduced the allowable variance in commercially available products and the lack of really knowing their true potency or concentration, i.e., if a commercial product has an allowable variance of 90 to 110%, we don�t really know if it is 92% or 109%,so we are at a disadvantage. Maybe the manufacturers should provide this information with the package? This difficulty is not generally presented when dealing with bulk drug substances.

Part II discussed potential errors in compounding from commercially available products used in intravenous admixtures; including overfill of additives and large volume vehicles, as well as using plastic syringes as �measuring devices� for compounding.

Part III will now discuss some variables that can occur at the analytical laboratory that may cause inaccurate results; we will begin by discussing the general process that occurs in an analytical laboratory.

First, the sample is received and logged in and appropriately labeled for tracking. Second, the sample is placed in proper storage conditions until analyzed. Third, the sample is removed from storage, allowed to equilibrate to room temperature and an analytical sample obtained from the bulk sample. Fourth, the sample may be pretreated and/or an extraction process conducted to remove the active drug (analyte) from the matrix in which it is contained. The matrix may be capsule contents, gelling agents, suspending agents, oils, ointment/cream vehicles, etc. In some cases, as in intrathecals, the matrix is much simpler to treat. Fifth, the extracted drug may require concentration or dilution to the appropriate range for the analytical method to be used. Sixth, the sample may be introduced into the instrument for analysis. Seventh, the response of the sample is compared to a reference standard and/or standard curve. Eighth, the results are then tabulated with the sample identification numbers and a report generated. This is a brief summary of the steps involved.

The next question to consider is, �Where can errors occur in an analytical laboratory?� The answer is, �Errors can occur in any of the above steps�. This week let�s just look at part of one step, the extraction method and its relationship to the final results.

Any laboratory that does testing must have a validated method for the drug AND drug dosage form that is being tested. For example, if a sample of dexamethasone injection, elixir, capsules, slow-release capsules, PLO gel, topical cream, troche, suppository or veterinary paste is being analyzed, the extraction of the dexamethasone is different in these cases. If the same extraction method is used, the quantity of dexamethasone actually extracted to form part of the analytical sample may vary. For example, the injection may not require extraction; the elixir may require extraction; the capsules, slow-release capsules, PLO gel, topical cream, troche, suppository and veterinary paste will require extraction. One extraction method is not necessarily appropriate for all these dosage forms because of the matrix. If only one extraction method is used and is not validated, the quantity of dexamethasone extracted from the regular capsule will be higher than that extracted from the slow-release capsule; consequently the final result will show that the slow-release capsule is sub-potent when it may be due to a faulty extraction method or the lack of accounting for the lower extraction efficiency in a slow-release matrix.

This is similar to blood level testing. The extraction of an analyte from blood, serum, plasma, etc. is not generally 100%. The laboratory will account for the extraction efficiency either by using standards that are prepared in the same matrix (blood, serum, plasma, etc.) or conducting studies where the extraction efficiency is known (i.e. 70%) and a final adjustment made to the results. The same is true for tissue samples and for all different matrices.

In our situation here, the analytical laboratory needs to know the formulation that is being analyzed so they will have the information needed to analyze the preparations properly. The laboratory also must validate the analytical method for the specific dosage form being used. Granted in many cases, the same method may work; for example, dexamethasone injection, dexamethasone iontophoresis solution, dexamethasone elixir; but it needs to be confirmed and considered. Obviously the most difficult cases involve the presence of polymers, such as in slow-release capsules, PLO gels, etc.; these are difficult to handle in a laboratory that is trying to provide rapid turnaround of samples for compounding pharmacies.

It is suggested that along with the sample being submitted, the exact formulation that was used also be submitted. Laboratories can keep this information confidential so it will not be given to others.

Next week, our continuing saga in why we need to know more about laboratory values before unquestioningly accepting them.

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

This service has been provided to pharmacists, technicians, students, pharmacy marketers, physicians, veterinarians and academicians around the world FREE of CHARGE.
There have been many topics discussed on the CNL in the last week, here are just a few:

• Sodium Tetradecyl Sulfate Injection � A pharmacists wanted a formula and help locating a lab to assay the preparation. The commercial product has been discontinued.
• Etodolac Topical � A pharmacist needed a formula and asked if it is stable in a PLO?
• Warfarin Suspension � A formula was needed. There was a discussion about stability and potency and a case report was given of a patient who was on the medication for one year.
• And many more too numerous to report here.

Here are a few of the articles featuring veterinary compounding that went on CompoundingToday.com�s literature abstract service:

• Andrew SE. Corneal fungal disease in small animals. Clin Tech Small Anim Pract 2003; 18(3): 186-192.
• Flecknell PA. Analgesia of small mammals. Veterinary Clin North Am Exot Anim Pract 2001; 4(1): 47-56, vi.
• Lust E. Compounding for animal patients: Contemporary issues. J Am Pharm Assoc (Wash DC) 2004; 44(3): 375-384.
• Moore CP. Immunomodulating agents. Vet Clin North Am Small Anim Pract 2004; 34(3): 725-737.
• Nieto JE, Spier S, Pipers FS. Stanley S, Aleman MR, Smith DC, Snyder JR. Comparison of paste and suspension formulations of omeprazole in the healing of gastric ulcers in racehorses in active training. J Am Vet Med Assoc 2002; 221(8): 1139-1143.

The personalized pharmaceutical services at North Heights Pharmacy & Compounding Center, 1201 E. 35th St., Texarkana, Ark., go far and beyond just filling prescriptions. Owner Cliff Robertson said their personal touch makes all the difference.
For full story, http://www.texarkanagazette.com/articles/2005/01/16/local_news/features/features14.txt

Testosterone makes the man, but what does it do for the woman? Gets her sex life simmering faster than the best paperback romance novel, advocates say
For full story, http://www.thestate.com/mld/thestate/living/health/10648042.htm

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