Determination of levamisole in urine by gas chromatography-mass spectrometry.

The United States Public Health Service Substance Abuse and Mental Health Services Administration is alerting medical professionals that a substantial percentage of cocaine imported into the United States is adulterated with levamisole, a veterinary pharmaceutical that can cause blood cell disorders such as severe neutropenia and agranulocytosis. Levamisole HCl is the active ingredient in a number of veterinary drugs approved to treat worm infestations in animals. Levamisole HCl was also the active ingredient in a human drug for oral administration approved on June 18, 1990, as adjuvant treatment in combination with fluorouracil after surgical resection in patients with Duke's stage C colon cancer. This drug was withdrawn from the U.S. market around 2000, and it has not been marketed in the U.S. since then. The objective of this study was to develop a method to determine the amount of levamisole in urine samples. The procedure will be provided to state health laboratories as needed to be used in the evaluation of patients that have developed neutropenia or agranulocytosis in the setting of recent cocaine use. A gas chromatography-mass spectrometry method was validated and tested at two different laboratories, and the method limit of detection for levamisole is 1 ng/mL in urine when using a 5-mL sample. Confirmation of the stereoisomer of levamisole was done by high-performance liquid chromatography using a chiral column.

Use of liquid chromatography-mass spectrometry and a chemical cleavage reaction for the structure elucidation of a new sildenafil analogue detected as an adulterant in an herbal dietary supplement.

An herbal dietary supplement, marketed as a natural product for the enhancement of sexual function, was analyzed by HPLC with photodiode array and mass spectral detection and found to contain a compound related to the synthetic phosphodiesterase-5 (PDE-5) inhibitors. Based on UV spectra, mass spectra and direct infusion MS(n), the structure of the compound was tentatively identified as a sildenafil analogue in which the sulfonyl group had been replaced with an acetyl group. This new analogue is similar to acetildenafil, a previously reported sildenafil analogue, but differs in that it contains an N-methyl group where acetildenafil contains an N-ethyl group. The structure of the unknown was unequivocally established by chemical cleavage of the phenacylamine group of the molecule to generate N-methylpiperazine; other cleavage products matched those generated from acetildenafil. Since the new compound has one less CH(2) group than acetildenafil, it was named nor-acetildenafil.

Structure elucidation of a novel analogue of sildenafil detected as an adulterant in an herbal dietary supplement.

A new analogue of sildenafil was detected in an herbal dietary supplement, which was sold over the internet and promoted as a product for the enhancement of sexual performance. The structure of the compound was established using LC-MS, UV spectroscopy, MS-MS, and NMR. In addition, the compound was cleaved at its sulfonamide S-N bond yielding a sulfonic acid and an amine, which were independently characterized using LC-MS, GC-MS, and derivatization. The compound, named methisosildenafil, is a novel synthetic analogue of sildenafil in which the N-methylpiperazine moiety has been replaced with 2,6-dimethylpiperazine.

Use of liquid chromatography-mass spectrometry and a hydrolytic technique for the detection and structure elucidation of a novel synthetic vardenafil designer drug added illegally to a "natural" herbal dietary supplement.

An herbal dietary supplement, marketed as a natural product for the enhancement of sexual function, was purchased covertly over the internet. The product was analyzed by LC-MS and found to contain a compound related to synthetic phosphodiesterase 5 (PDE-5) inhibitors. Based on LC with photodiode array and mass spectral detection, along with collision-induced dissociation-mass spectral analysis, the structure of the compound was tentatively identified as a designer drug of vardenafil in which the N-ethylpiperazine ring had been replaced by a piperidine ring. This structure was unambiguously confirmed by acid hydrolysis of both the unknown ("piperidenafil") and vardenafil and comparison of their hydrolysis products by LC-MS and GC-MS. The hydrolytic technique proved to be a useful tool for the structure elucidation of piperidenafil and may be a useful technique for the structure elucidation of other erectile dysfunction designer drugs in the future. The dosage level of piperidenafil in the herbal product was 41 mg per capsule when calculated as the free base.