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Biomedical subjects

G Petzinger

Publications and source records attributed to G Petzinger.

At least 19 recordsLinked to original sources
PubMed2001

Isolation of a 2:1 hydrochlorothiazide-formaldehyde adduct impurity in hydrochlorothiazide drug substance by preparative chromatography and characterization by electrospray ionization LC-MS.

Hydrochlorothiazide drug substance (19 lots) from five different manufacturers and four different countries of origin (USA, Italy, Hungary, and Croatia) were analyzed for the presence of impurities using a gradient elution chromatographic system, with acetonitrile-water as the mobile phase. Two known impurities of hydrochlorothiazide, 4-amino-6-chloro-1,3-benzenedisulfonamide and chlorothiazide, were separated, as well as a late-eluting, unknown, recurring impurity. The unknown impurity was isolated by preparative liquid chromatography followed by preparative thin-layer chromatography. It was characterized by electrospray ionization LC-MS as a 2:1 hydrochlorothiazide-formaldehyde adduct of the parent drug substance. The adduct is believed to form through the double condensation reaction of hydrochlorothiazide with excess formaldehyde during the parent compound's synthesis. The concentration of this impurity ranged from 0.02 to 1.1% (area%), and was above the 0.1% USP Other Impurities threshold in 16 of the 19 lots examined.

Antihypertensive Agents↗
PubMed2000

Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model.

Presynaptic denervation is likely to play an important role in the pathophysiology of dyskinesias that develop after levodopa administration to patients with Parkinson's disease. In this study, the thresholds of nigrostriatal damage necessary for the occurrence of parkinsonism and levodopa-induced involuntary movements were compared in squirrel monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals treated with a regimen of MPTP that caused parkinsonism displayed > or =95% striatal dopamine depletion, 90% reduction of striatal dopamine uptake sites, and 70% nigral neuronal loss. Levodopa administration ameliorated the parkinsonian signs of these monkeys but also induced dyskinesias. A separate group of animals was treated with a milder MPTP regimen that caused 60%-70% striatal dopamine depletion, a 50% decrease in dopamine transporter, and 40% loss of dopaminergic nigral neurons. While these monkeys displayed no behavioral signs of parkinsonism, they all became dyskinetic after levodopa administration. The priming effect of levodopa, that is, the recurrence of dyskinesias in animals previously exposed to the drug, was compared in severely versus mildly lesioned monkeys. When severely injured parkinsonian animals underwent a second cycle of levodopa treatment, they immediately and consistently developed involuntary movements. In contrast, the recurrence of dyskinesias in primed monkeys with a partial nigrostriatal lesion required several levodopa administrations and remained relatively sporadic. The data indicate that moderate nigrostriatal damage which does not induce clinical parkinsonism predisposes to levodopa-induced dyskinesias. Once dyskinesias have been induced, the severity of denervation may enhance the sensitivity to subsequent levodopa exposures.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Investigating levodopa-induced dyskinesias in the parkinsonian primate.

Research into the cause of dyskinesias arising from levodopa treatment has been vexingly limited, partly due to the lack of an inexpensive and widely available animal model. Rodents do not develop levodopa-induced dyskinesias in a clinically recognizable form. However, nonhuman primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism readily develop levodopa-induced dyskinesias that are virtually indistinguishable from those seen in patients with Parkinson's disease. We have developed and validated a five-point Global Primate Dyskinesia Rating Scale to accurately measure these dyskinesias. Monkeys with MPTP-induced parkinsonism were then investigated to evaluate the relationship between dyskinesias, parkinsonism and severity of the nigrostriatal lesion. All parkinsonian animals were responsive to levodopa, and developed dyskinesias within 2-3 days of levodopa administration. Monkeys treated with only a single injection of MPTP also developed dyskinesias, even though they were not parkinsonian. It would appear that there is a different threshold of striatal dopamine depletion for parkinsonism and dyskinesias in the monkey. Finally, three hypotheses, put forward to explain the genesis of dyskinesias, are reviewed, and various experimental approaches suggested for each.

Animals↗
PubMed1999

Isolation and identification of process impurities in trimethoprim drug substance by high-performance liquid chromatography, atmospheric pressure chemical ionization liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy.

Twenty-two lots of recently synthesized trimethoprim drug substance, from five different manufacturers, in three different countries of origin, China, Israel and the United States, were investigated for the presence of impurities. A liquid chromatographic system, using gradient elution, and a mobile phase consisting of 0.25% TEA/0.1% formic acid (pH 5.8)--acetonitrile, was used to separate and detect two significant, recurring impurities in trimethoprim drug substance. The two impurities were isolated by preparative liquid chromatography and identified, using a combination of liquid chromatography/mass spectroscopy and nuclear magnetic resonance, as 2,4-diamino-5-(4-ethoxy-3,5-dimethoxybenzyl) pyrimidine and 2,4-diamino-5-(3-bromo-4,5-dimethoxybenzyl) pyrimidine. These impurities were not detected by the compendial method and were present at significant levels in 17 of the lots tested. Total impurity concentrations were in the range of 0.1-2.1%.

Atmospheric Pressure↗
PubMed1996

Use of intrathecal baclofen in the treatment of patients with dystonia.

BACKGROUND: Continuous infusion of intrathecal (IT) baclofen is a highly effective standard therapy for severe spasticity of spinal origin. By contrast, there is limited clinical experience regarding the use of IT baclofen in treating patients with dystonia, and little is known regarding the indications for treatment, efficacy, and safety of IT baclofen in this disorder. OBJECTIVE: To study retrospectively the effects of IT baclofen in treating 25 patients with severe segmental or generalized dystonia. SETTING: Neurological Institute, Columbia-Presbyterian Medical Center, New York, NY. PATIENTS: Twenty-five patients with severe segmental or generalized dystonia that was refractory to oral medications underwent IT baclofen test dosing. In addition to dystonia, 17 patients had spasticity or painful spasms. Thirteen of 25 patients responded to the test doses of IT baclofen, according to unblinded neurological assessments that included the patient's subjective report; all 13 underwent implantation of a pump for continuous IT baclofen infusion. RESULTS: In contrast to reports of patients with spasticity of spinal origin, those with dystonia in the present series had a lower response rate to bolus IT baclofen doses and a smaller degree of clinical improvement. For 10 of the 13 responders to the test doses of IT baclofen, dystonia rating scale scores of videotaped examinations by blinded observers detected no significant change (P < .07) in severity of dystonia. Retrospective data from 11 of 13 patients with implantable pumps, followed up for a mean interval of 21 months after pump insertion, showed continuing efficacy in 6 individuals (55%), based on a determination of patient satisfaction; however, only 3 patients (27%) reported a sustained improvement in functional capacity. Five (38%) of the 13 patients with implantable pumps experienced severe complications that required hospitalization. CONCLUSIONS: Despite recent reports that have described the benefit in small numbers of patients with dystonia, we concluded that the role of IT baclofen in treating severe dystonia remains uncertain. Intrathecal baclofen may be more effective when dystonia is associated with spasticity or pain. In the present series, we detected no significant difference in the response to IT baclofen in patients with or without spasticity or pain, perhaps owing to the small sample size.

Baclofen↗
PubMed1996

GC/MS comparison of the West Indian aphrodisiac "Love Stone" to the Chinese medication "chan su": bufotenine and related bufadienolides.

The death of a 23-year-old man resulting from digoxin-like toxicity and heart failure was attributed to ingestion of a West Indian aphrodisiac known as "Love Stone." GC/MS analyses identified bufotenine, a controlled substance under both US and New York State statutes. In addition, a series of bufadienolides, namely resibufogenin, bufalin, and cinobufagin, were also identified. Bufadienolides, which are derived from toad venom or secretions, are cardiotonic steroids that cause symptoms similar to digoxin. GC/MS analyses of the Chinese medication "Chan Su," a product derived from toads, produced a highly similar elution profile and contained the same compounds as "Love Stone." The data demonstrate that the aphrodisiac was also derived from toads.

Adult↗
PubMed1990

Potential misidentification of trichlorophenylethanol in imported peppers.

During regulatory analyses for the determination of pesticide residues on agricultural commodities, a frequently encountered trichlorinated compound was misidentified by the NBS library search routine. This case history illustrates the need for more rigorous confirmation criteria when dealing with multi-chlorinated compounds where fragmentation can be dominated by methyl loss followed by loss of CO and HCI.

Benzyl Alcohols↗
PubMed1983

Application of mass spectrometry in the regulatory analysis of pesticides and industrial chemicals in food and feed commodities.

During regulatory analysis of pesticides and industrial chemicals, compounds are frequently encountered which cannot be readily identified by gas chromatography alone on two or more stationary phases. Such incurred unknown analytical responses are examined by gas chromatography mass spectrometry, particularly if they have been shown to contain P, S, N or halogen via specific gas chromatography detectors. Seven case histories are presented to illustrate the analytical approach adopted to structurally elucidate such compounds at the ppm level. These examples demonstrate the potential complementary combination provided by low resolution electron impact and chemical ionization mass spectrometry in structural determinations.

Animal Feed↗
PubMed1981

Colorimetric determination of disulfiram in tablets: collaborative study.

The colorimetric reaction of cuprous iodide and disulfiram has been collaboratively studied in 8 laboratories to determine the drug in tablet form at 2 dosage levels. The disulfiram was extracted from the tablet matrix with methylene chloride. After a basic wash with 1 M NaOH, an aliquot of the methylene chloride solution was reacted with solid cuprous iodide, and the absorbance of the resulting color was measured. Single assays on 2 synthetic preparations of known disulfiram content were performed with average recoveries of 98.4 and 99.2% for 93.3 and 105.3 mg, respectively. Duplicate determinations on 2 commercial tablet preparations declared at 250 and 500 mg gave mean and standard deviation values of 246.6 +/- 6.40 and 493.6 +/- 12.0 mg, respectively. The results agreed closely with those obtained by the author using the NF iodometric titration procedure. The method has been adopted official first action.

Chromatography, Thin Layer↗