J AAPOS. 1999 Feb;3(1):53-7.
Pediatric tetracycline-induced pseudotumor cerbri.

Quinn AG, Singer SB, Buncic JR.

Department of Ophthalmology, The Hospital For Sick Children, University of Toronto, Ontario, Canada.

BACKGROUND: Tetracyclines have long been recognized as a cause of pseudotumor cerebri in adults, but the role of tetracyclines in the pediatric age group has not been well characterized in the literature and there have been few reported cases. We present 6 cases to better delineate the problem, the patient profile, the response to treatment, and the sequelae. METHODS: We retrospectively analyzed the records of all patients admitted with a diagnosis of pseudotumor cerebri who had documented usage of a tetracycline-class drug immediately before presentation at the Hospital For Sick Children in Toronto, Canada, from January 1, 1986, to March 1, 1996. RESULTS: Six patients (5 female, 1 male) who met all inclusion and exclusion criteria were identified; their ages ranged from 12 to 17 years. All were being treated for acne vulgaris. Duration of use before diagnosis was as short as 2 weeks and as long as 10 months, with a mean of 4.4 months. Duration of symptoms ranged from 0.57 to 4 weeks. Symptoms included headache (6 of 6), nausea (5 of 6), and diplopia (4 of 6). All for whom height and weight data were known (5 of 6) were in the upper quartile for body mass index. Visual acuity was 6/6 in all but 1 eye of one patient (6/9) at diagnosis, and final visual acuity was 6/6 in all patients. All had normal color vision, where this was recorded (5 of 6). The only recorded field defect was enlargement of the blind spot (4 of 6). All patients responded to treatment, with loss of symptoms in 1 day to 4 weeks. CONCLUSIONS: Pseudotumor cerebri as a result of tetracycline-class drugs does occur in the pediatric population. With prompt and appropriate medical treatment, long-term sequelae can almost always be avoided. Physicians who treat patients with tetracyclines need to be aware of the potential complications in children.

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rug.ac.be

A novel, sensitive, high performance liquid chromatography/tandem mass spectrometric (i.e. mass spectrometry/mass spectrometry) method with on-line extraction and clean-up for the screening and confirmation of residues of tetracyclines in kidney has been developed. After liquid extraction of homogenised kidney with McIlvain buffer, an aliquot of the extract is directly injected on the LC/MS/MS system with further extraction and clean-up of the sample on-line. Detection of the analytes was achieved by positive electrospray ionization followed by multiple reaction monitoring. For each tetracycline the collisional decomposition of the protonated molecule to a unique, abundant fragment ion was monitored. The method has been validated for tetracycline, oxytetracycline, chlortetracycline and doxycycline. Calibration curves resulting from spiked blank kidney samples at the 100-1200 microgram/kg level showed good linear correlation. At the level of 600 microgram/kg both within- and between-day precision, as measured by relative standard deviation (RSD), were less than 7%. The limits of detection (LODs) for tetracycline, oxytetracycline, chlortetracycline and doxycyline were 18, 23, 24 and 21 microgram/kg, respectively. The limits of quantification (LOQs) for tetracycline, oxytetracycline, chlortetracycline and doxycyline were 36, 46, 47 and 42 microgram/kg, respectively. The recoveries ranged from 71 to 91%. The procedure provides a rapid, reliable and sensitive method for the determination of residues of tetracyclines in bovine kidney. The advantage of this method over existing methods is its decreased sample preparation and analysis time, which makes the method more suitable for routine analysis. Copyright 2000 John Wiley & Sons, Ltd.

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lpsi.barc.usda.gov

A simplified procedure was developed for determination of tetracycline antibiotics in tissues which improved stability of these compounds in sample extracts and eliminated the need for troublesome cleanup procedures. Tissues were homogenized in water. Acetonitrile (16 mL) and then 1 mL of 0.1 M H(3)PO(4) were added to 4 mL of homogenate and the clear supernatant was filtered. The filtrate was mixed with hexane and dichloromethane and the resulting water layer was collected, evaporated to 1-2 mL, and filtered into autosampler vials. Ion-pairing liquid chromatography was used to separate tetracyclines from interferences in sample extracts, eliminating the need for further cleanup. Analysis was isocratic using a Phenomonex Prodigy ODS(3) column with a mobile phase of 4 mM oxalic acid, 4 mM sodium oxalate, 10 mM sodium decanesulfonate-acetonitrile (70 + 30 for oxytetracycline and tetracycline; 66 + 34 for chlortetracycline). Recoveries were generally in the 90-100% range with limits of quantitation of 0. 05-0.1 ppm. The procedure was evaluated with beef and pork muscle, liver, and kidney.

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J Agric Food Chem. 2001 Apr;49(4):1669-74.
Determination of tetracycline and streptomycin in mixed fungicide products by capillary zone electrophoresis.

Hsiao YM, Ko JL, Lo CC.

Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Number 11, Kuang Ming Road, Wufeng, Taichung Hsien, Taiwan, Republic of China.

A method of capillary zone electrophoresis (CZE) was used to determine tetracycline and streptomycin content in commercial agriculture products. The results indicated that this method was capable of analyzing the mixed fungicide in formulated products with instrument detection limit (IDL) of 0.50 microg/mL and a method detection limit (MDL) of 0.52 microg/mL for tetracycline, and IDL of 1.00 microg/mL and MDL of 1.22 microg/mL for streptomycin. Precision expressed by relative standard deviation (RSD) ranged from 1.44 to 4.37% of tetracycline and 1.00 to 4.20% of streptomycin. Recoveries were in the region of 98.2-102.5% for tetracycline and 95.3--103.0% for streptomycin. The low detection limit, the low RSD values, and the high percentage of recovery confirmed that the CZE technique is a sensitive and selective method. And the CZE method can analyze both tetracycline and streptomycin at the same time without complicated extraction and further derivative reaction.

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J Chromatogr. 1992 Apr 10;596(2):211-6.
Determination of tetracyclines in bovine and porcine muscle by high-performance liquid chromatography using solid-phase extraction.

Walsh JR, Walker LV, Webber JJ.

Regional Veterinary Laboratory, Department of Agriculture, Hamilton, Victoria, Australia.

A method is presented for the determination of the three tetracyclines oxytetracycline, tetracycline and chlortetracycline in muscle, spiked at 100 ng/g, using high-performance liquid chromatography (HPLC). The concentration and extraction steps are carried out using Waters Environmental Sep-Pak cartridges. The principal steps involve homogenizing the sample in EDTA-McIlvaine buffer followed by centrifugation and precipitation of the supernatant using trichloroacetic acid. After further filtration and concentration on a Sep-Pak cartridge, the sample is eluted and analysed by HPLC with UV detection and confirmation by diode-array. The column used is a Nova-Pak C18 (4 microns) cartridge (10 cm x 8 mm I.D.). A phosphate-citrate-acetonitrile buffer, utilizing ion suppression, is the mobile phase. The analytes are detectable at levels down to 10 ng/g. The analyte identity can be confirmed at 20 ng/g by the use of diode-array detection and spectral library comparison.

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J Chromatogr. 1992 Oct 9;623(1):153-8.
Determination of tetracycline antibiotics by reversed-phase high-performance liquid chromatography with fluorescence detection.

Iwaki K, Okumura N, Yamazaki M.

School of Pharmacy, Hokuriku University, Ishikawa, Japan.

A highly sensitive method for the determination of tetracycline antibiotics (TCs) using reversed-phase high-performance liquid chromatography with fluorescence detection is presented. This method was based on the use of disodium ethylenediaminetetraacetate (EDTA) and calcium chloride as fluorescence-increasing reagents in the mobile phase. The concentrations of each reagent in the mobile phase greatly influenced the fluorescence intensity of TCs. When the concentration of EDTA and calcium chloride were 25 and 35 mM, respectively, and the pH of the mobile phase was 6.5, the maximum fluorescence intensity was obtained. The column temperature hardly influenced the fluorescence intensity. At 3.75 ng of TCs injected, the precision (relative standard deviation) ranged from 1.12 to 2.20%. In the range 0.075-37.5 ng for tetracycline and oxytetracycline and 0.225-37.5 ng for chlortetracycline, a linear response was observed. The detection limits of this method were 49-190 pg for three different TCs. The proposed method was applied to the determination of one of the TCs in pharmaceuticals by the internal standard method using other TCs as internal standards and was also applied to determination of TCs added to fish tissue.

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J Pharm Sci. 1988 Jan;77(1):78-80.
Determination of tetracycline hydrochloride in presence of anhydrotetracycline by differential pulse polarography.

Sabharwal S, Kishore K, Moorthy PN.

Bhabha Atomic Research Centre, Nuclear Research Laboratory, Kashmir, India.

A differential pulse polarographic method is described for the determination of the antibiotic tetracycline HCl in the presence of its degradation product anhydrotetracycline. The method utilizes the large difference in their differential pulse polarograms at a peak potential of -1.39 V in 0.1 M phosphate buffer as the base electrolyte (pH 6.8). The assay was evaluated using synthetic mixtures and applied to the analysis of commercial tetracycline HCl samples. The results obtained with this method are in close agreement with those from the spectrophotometric absorbance ratio method.

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Cell. 1978 Jan;13(1):73-81.
On the nature of tetracycline resistance controlled by the plasmid pSC101.

Tait RC, Boyer HW.

In vitro enzymatic alteration of plasmid phenotype and in vitro construction of recombinant plasmids containing genetic information derived from the plasmid pSC101 have been used to investigate the mechanism of function of tetracycline resistance determined by the plasmid pSC101. The resistance has been shown to be inducible and involves the increased synthesis of membrane-associated polypeptides of 34,000, 26,000 and 14,000 daltons that are encoded for by the plasmid. The 34,000 dalton polypeptide along with another plasmid-encoded polypeptide of 18,000 daltons function in an ATP-independent manner to prevent the accumulation of tetracycline by the cell. These polypeptides are sufficient for resistance. A second component of plasmid-determined resistance involves the 14,000 dalton polypeptide and reduces the initial adsorption of tetracycline by sensitive cells, but is not alone sufficient for the generation of resistance. The role of the 26,000 dalton polypeptide in tetracycline resistance has not been identified.

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