Francis M. Urry

Procedure for the Monitoring of Gabapentin with 2,4,6-Trinitrobenzene Sulfonic Acid Derivatization Followed by HPLC with Ultraviolet Detection

Gabapentin is a novel anticonvulsant drug that was introduced in the early 1990s and later approved (1995) for use in the US as an adjunctive treatment of partial seizures with or without secondary generalization in persons >3 years of age. Although structurally similar to γ-aminobutyric acid (GABA), gabapentin does not interact with GABA receptors, nor is it converted to GABA or a GABA agonist (1). Gabapentin is widely studied therapeutically. Its initial and approved use as adjunctive epileptic therapy has been broadened, with many additional indications. These include treatment for neuropathic pain after spinal cord injury (2)(3)(4), posttraumatic stress disorder (5), poststroke pain syndrome (6)(7)(8), alcohol withdrawal(9), migraine therapy (10), hot flashes associated with prostate cancer treatment (11), and postoperative pain after cancer surgery (12)(13). The general mechanism by which gabapentin exerts its anticonvulsant action is unknown. It is not appreciably metabolized in the liver, nor does it induce liver enzymes. It circulates relatively unbound in serum, with a protein bound fraction of ∼3%. It has a volume of distribution of ∼58 L. Because gabapentin does not bind to protein, it can be removed by hemodialysis if medically necessary. Gabapentin is renally eliminated with an elimination half-life of ∼6 h and clearance proportional to creatinine clearance. Impaired renal function substantially decreases the clearance of gabapentin (14). Gabapentin exhibits saturable absorption, making it a nonlinear drug and kinetically less predictable. A dose–response pattern is apparent for plasma gabapentin concentrations and for clinical effects within the dosage range 600-1800 mg/day. Seizure control has not been seen with trough plasma concentrations <2 mg/L. A majority of patients at suggested doses fall within a 2–10 mg/L range. The major side effects of the drug include somnolence, dizziness, ataxia, fatigue, and nystagmus. No …

Comparison of sample preservation methods for clinical trace element analysis by inductively coupled plasma mass spectrometry.

The effects of chemical additives and storage temperatures on measurement of 16 trace elements in urine by inductively coupled plasma mass spectrometry (ICP-MS) were evaluated. A 24-hour urine specimen was supplemented with concentrations of the elements. Aliquots containing 1 of 4 chemical additives were stored at 3 different temperatures in sealed polypropylene containers. Elemental concentrations were determined by ICP-MS for the resulting samples after 1, 2, 8, and 65 days of storage. Initial element concentrations measured within 8 hours of specimen preparation were consistent with expected concentrations (except for aluminum). For most elements, preservation and storage conditions yielded consistent measured concentrations throughout the experiment. Notable exceptions were for aluminum (general rise over time) and mercury (general decrease over time). Adding boric acid and potassium pyrosulfate resulted in sample contamination; elemental contamination was concentration-dependent for both. Although little microbial contamination was observed during the experiment, refrigeration of samples is recommended to curtail bacterial growth in nonsterile specimens. In light of these results, refrigerated urine storage without the use of chemical additives is an effective preservation method for ICP-MS analysis of many trace elements.