Nitrite Adulteration of Workplace Urine Drug-Testing Specimens I ...

More documents

Recommendations

Info

industry, through biological processes of nature and agricultural practices, nitrate and nitrite occur in food, water, and air. \~en these items are consumed, nitrite may appear in the urine. Food. Nitrate and nitrite salts are used as a preservative of meats to delay decomposition and maintain color for consumer appeal. Their concentration as a food additive is low, at 50-200 parts per million. Some vegetables, such as spinach, lettuce, celery, and potatoes, are particularly nitrate-rich. Consumption of vegetables and nitrite-preserved foods result in nitrite inges- tion of 0.8-8.4 m~day (18). Under normal gastrointestinal conditions, most of the ingested nitrite is destroyed by food and gastric juices (19) and by oxygenated hemoglobin in the red blood cells as described. Vegetables and preserved meats would contribute less than 1 IJg/mL nitrite to the urine. Water Nitrate in drinking water, which is largely florn runoff flom agricultural use of nitrate-containing fertilizers, is a recog- nized public health issue. Nitrate in drinking water can produce methemoglobinemia (through formation of nitrite), which is a serious condition for newborn and very young infants. In the United States, the EPA enforces a maximum contaminant level (MCL) of 10.2 m~L of nitrogen as nitrate plus nitrite, and an MCL of 1 m~L of nitrite nitrogen (20). Assuming a daily consumption of 3 L of drinking water, and a reduction of nitrite in the stomach, the portion of nitrite in urine originating from drinking water 92 Table II. Nitrite Concentrations in Urine Specimens from Patients Receiving Organic Nitrate/Nitro/Azo Medications* Medication Nitrite (pg/mL) Medication Nitrite (pg/mL) Nitroglycerin
Jourr, al of Analytical Toxicology, Vol. 22, March/April 1998 Metronidazole was of interest because it can be given in doses as high as 4 g/day. Of the two patients on metronidazole, one was receiving 1.5 g/day, which produced 0.8 IJg/mL nitrite. Ranitidine resulted in a similar level of nitrite in the urine. The urinary tract analgesic phenazopyridine was included. Although not containing a nitro group, it was tested because the Chemstrip package insert indicated that it might give a false-positive reading for nitrite because of the orange-red color it imparts to the urine (15). The modestly increased apparent nitrite concentration with phenazopyridine listed in Table II may be due to color from phenazopyridine. Specimens from patients taking antifungal and antineoplastic drugs were not tested. The antifungal drugs are applied topically, and relatively little would reach the urine. With antineoplastic agents, the daily dosage does not exceed 300 mg of parent drug, and it would not increase urinary nitrite beyond a few nanograms per milliliter. Medical care: Medications which stimulate the in vivo formation of nitrite~nitrate through induction of NOS. ]ndomethacin transfusion for premature infants lead to a 25- fold increase in urine nitrite concentration through a currently unknown mechanism (26). The increase returned to baseline after 3 days, indicating that this was a transitory effect not related to chronic administration. In order to assess the possible effect of indomethacin in a workplace setting, two male subjecL~ of working age were given a standard dose of indomethacin (25 rng three times per day) with specimens taken at 2, 8, 12, 24, and 48 h after the initial dose. All specimens from both subjects had a nitrite concentration below the limit of detection of the method, 0.6 lJg/mL. No effect was observed. lnterleukin-2 in cancer treatment can increase urinary Table III. Nitrite Concentrations in Urine Specimens Received for Employment Drug Testing which Appeared to Have Been Adulterated With Excess Nitrite Specimen No. Nitrite (pg/mL) Specimen No. Nitrite (pg/mL) A* 3640 + 17 5490 1 1910 18 6300 2 4400 19 4200 3 7390 20 7030 4 10,700 21 4140 5 6770 22 4530 6 4400 23 2500 7 11,500 24 11,600 8 5420 25 7780 9 12,200 26 6730 10 8340 27 7750 11 6930 28 4040 12 4630 29 4990 13 3810 30 4140 14 3740 31 6540 15 4070 32 2920 16 4560 Average 59 I0 Range 1910-12,200 * Certified drug-negative urir+e i)(x)l, negative by lest strip for nitrite, fotlified with one vial of Klear in 50 mL urine. r Results rounded to three significant figures because of 1000+f(~kl dilution of specimet~s. nitrate and nitrite through the induction of cytokines and NOS (27). This study produced a peak urine nitrate concentration of 183 tJg/mL. Intentional addition to the urine after voiding "Fable III lists the concentrations of nitrite found in ~outine workplace drug-testing specimens which presented to the laboratory with a pattern consistent with adulteration: an initial test positive (for cannabinoids), a failure to confirm by GC-MS due to little or no recovery of the ions of 9-THCA and its deuter- ated internal standard, and a strongly positive reaction for nitrite on the Chemstrip. A clinical specimen being screened for a urinary tract infection produces a light pink color on the Chem- strip. A specimen to which Klear has been added (or crystalline potassium nitrite for experimental purposes) produces a vivid red-violet color that persists for approximately 20 s and then fades to a pale orange. Each microtube of Klear contains about 500 mg of potassium nitrite. With a minimal acceptable urine volume of 30 mL, an estimated maximum volume of 120 mL (as may occur in a split specimen collection using a collection con- tainer), a variable percent purity of potassium nitrite (85-96%+), and the potential for addition of either one or two microtubes of Klear, a urine specimen to which Klear was added would be expected to contain between 1900 and 15,000 IJg/mL nitrite. The 32 specimens suspected of nitrite adulteration ranged from a low of 1910 to a high of 12,200 1Jg/mL with an average of 5910. None of the 32 specimens had a concentration less than 1500 IJg/mL. Specimen A was prepared in the laboratory by adding one microtube of Klear to 50 mL of certified drug-free urine that was negative for nitrite with the Chemstrip. It produced a nitrite concentration of 3640 IJg/mL. Background nitrite concentration in drug-negative specimens In order to assess background levels of nitrite in urine specimens for workplace drug testing, specimens which were initial test negative were evaluated. From among 200 specimens which were tested by the Chemstrip, 15 were selected as producing the most color on the Chemstrip (Note: none of the 200 produced the typical intense pattern of nitrite adulteration). These specimens were stored at room temperature for 2 weeks, and then tested for nitrite concentration. They were held an additional 6 days and retested. This process, although uncharac- teristic of holding times and conditions for employment testing specimens, was used to represent an extreme circumstance in the amount of background nitrite that might be found in a negative workplace drug-testing specimen. The data are displayed in Table IV. On the first test (2 weeks from collection), the group averaged 50.2 IJg/mL with a range of 6.2-128.1. The data on the retest were very similar. The maximum nitrite concentration obtained was 129.1 IJg/mL, which was the highest concentration obtained in the entire 93
Page 1 and 2: Journal of Analytical Toxicology, V
Page 3: Journal of Analytical Toxicology, V
Page 7: Journal of Analytical Toxicology, V

Nitrite Adulteration of Workplace Urine Drug-Testing Specimens I ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?