Microsoft powerpoint - 2008 asra poster - hmn

Stability of Ziconotide with other medications including Hydromorphone Hydrochloride,
Clonidine and Baclofen in intrathecal pumps in advanced Pancoast tumor
Hany M. Nasr, M.D.*, Nashaat N. Rizk, M.D.*, Matthew D. Krasowski, M.D., Ph.D.† University of Pittsburgh School of Medicine *Department of Anesthesiology; †Department of Pathology The matrix for the MALDI-ToF analysis was prepared as follows: INTRODUCTION
alpha-cyano-four-hydroxycinnamic acid was dissolved in 1:1 (v/v) acetonitrite/H2O supplemented with 0.1% trifluoroacetic acid in order to obtain a saturated solution. Samples mixed with the matrix Intrathecal pumps have been used in patients with chronic solution was placed on a sample plate and allowed to dry for five abdominal pain for various diagnoses. We describe a case where minutes. Positive ion MALDI-ToF-MS in the reflector mode was the stability of Ziconotide was tested with multiple medication s performed on a Voyager Pro DE MALDI-ToF mass spectrometer including intrathecal hydromorphone hydrochloride, bupivacaine (Applied Biosystems, Framingham, MA, USA) at the University of and baclofen , as a complex multidrugs admixture.
Pittsburgh Proteomics Core facility.
To our knowledge this hasn’t been tested previously except with CASE REPORT
To examine the stability of the peptide drug during the time in the A 58-year-old male presents with right upper extremity patient’s intrathecal pump, the residual fluid in the patient’s radiculopathy as a result of right sided Pancoast tumor compressing intrathecal pump was compared by MALDI-MS with a solution of on the right brachial plexus. Of note, the patient, who failed a series pump fluid prepared to be identical to that originally instilled into of cervical epidural injection in maintaining pain relief, has also the patient’s pump. For simplicity, the two solutions will be referred metastases to the ninth rib. The patient was on numerous to as “patient sample” and “control sample.” We were especially medications including fentanyl patch, acetaminophen/hydrocodone, interested in testing four possibilities: (1) the peptide drug has oxycodone, pregabalin, duloxetine hydrochloride and gabapentin. degraded in the patient sample to smaller fragments, (2) adducts Patient sustained numerous side effects including nausea, vomiting, between the other drugs in the pump fluid and ziconotide had dizziness and constipation which interfered with the patient activity formed, (3) polymers of ziconotide had formed in the patient of daily livings. Patient had an intrathecal pump trial with promising sample, and (4) one or more of the three disulfide bonds of results followed by permanent implantation with a total of 0.1 mg of morphine, 1 mcg of clonidine, 2 mcg of baclofen and 0.05 mg of Analysis of the MALDI-MS spectra, scanning over a wide m/z range, bupivacaine hydrochloride per ml. Dose were titrated up 3.2 mg of showed no evidence of ziconotide fragmentation, adduct formation, morphine, 102.4 mcg of baclofen, 44.8 mcg of clonidine and 0.966 or polymerization. The only ions identified were the intact peptide mg of bupivacaine in a total of 24 hours with good relief of pain, and ions likely corresponding to oxidized and de-oxygenated forms followed by progressively increasing pain in the right chest wall and of ziconotide. Simplified m/z spectra of the patient and control abdomen. The rate was increased by 10-15 % with the use of oral samples are shown in figure 1A and 1B.
transmucosal fentanyl citrate for breakthrough pain as needed with minimal improvement in the VAS scale 7/10 and the patient functional status. Patient continued to experience pain at the higher pump settings. Consequently, intrathecal ziconotide (12.5 mcg/ml) DISCUSSION
was added to hydromorphone (2.0 mg/ml), baclofen (300.0 mcg/ml) and bupivacaine (7.5mg/ml) with improvement of the patient’s functional status and VAS 3/10.
Using mass spectrometry, the addition of baclofen, hydromorphone hydrochloride and bupivacaine to ziconotide has not altered the stability of the protein peptide after forty days in the intrathecal The intrathecal pump fluid samples were extracted by using a C18 Sep-Pak solid–phase column to help separate the peptide from the REFERENCES
salts and other constituents of the pump fluid. The protein was eluted off the column with a 4:1 (v/v) methanol:water solution. We subjected the samples to matrix-assisted laser desorption 1.Shields D, Montenegro R, Ragusa M. Chemical stability of ionization-time of flight mass spectrometry (MALDI-ToF-MS), a admixtures combining Ziconotide with morphine or technique that can analyze with high precision and accuracy the hydromorphone during simulated Intrathecal administration. molecular weight of the molecules in the pump fluid. MALDI-MS Neuromodulation 2005;8(4):257-263.
involves bombardment of samples molecules with a laser light to 2.Wermeling DP, Berger JR. Ziconotide Infusion for Severe Chronic bring about sample ionization (acquisition of charge). The sample is Pain: Case Series of Patients with Neuropathic Pain. pre-mixed with a highly absorbing matrix (e.g., alpha-cyano-4- Pharmacotherapy 2006;26(3):395-402.
hydroxycinnamic acid) that converts laser energy into excitation energy. MALDI-MS is excellent for non-volatile molecules such as peptides. The output is an analysis of signal intensity versus the mass/charge (m/z) ratio. Most molecules are singly charged so that the m/z ratio is equal to the molecular weight of the ion.

Source: http://www.pain.pitt.edu/paincontent/news/2008%20ASRA%20Poster.pdf