Chemistry: analytical and immunological testing – Heterocyclic carbon compound – Hetero-n
Reexamination Certificate
2001-09-05
2004-03-30
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Heterocyclic carbon compound
Hetero-n
C436S106000, C436S164000, C436S815000, C436S901000
Reexamination Certificate
active
06713306
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is concerned with a method for identification of a date rape drug. Specifically, the invention is a method for the qualitative identification of flunitrazepam in a sample such as a beverage.
Flunitrazepam is a member of the benzodiazepine class of drugs and is marketed under the brand name ROHYPNOL. Flunitrazepam has never been approved for medical use in the United States, therefore, doctors cannot prescribe it and pharmacists cannot sell it. However, it is legally prescribed in over 50 other countries and it is widely available in Mexico, Colombia, and Europe where it is used in the treatment of insomnia and as a pre-anesthetic. Unfortunately, flunitrazepam has become a popular illicit drug in the United States and is commonly known in the illegal drug trade as roofies, roach, or rope.
Like other benzodiazepines (such as those distributed under the brand names VALIUM, LIBRIUM, XANAX and HALCION), flunitrazepam's pharmacological effects include sedation, muscle relaxation, reduction in anxiety and prevention of convulsions. However, flunitrazepam's sedative effects are approximately 7 to 10 times more potent than diazepam (VALIUM). The effects of flunitrazepam appear approximately 15 to 20 minutes after administration and last approximately 4 to 6 hours. Some residual effects can be found 12 hours or more after administration.
Flunitrazepam causes partial amnesia; individuals are often unable to remember certain events that they experience while under the influence of the drug. This effect is particularly dangerous when flunitrazepam is used to aid in the commission of sexual assault. Victims may not be able to clearly recall the assault, the assailant, or the events surrounding the assault. It is difficult to estimate how many flunitrazepam-facilitated rapes have occurred in the United States. This problem is the direct result of the amnesia induced by the drug which causes the victim to be uncertain about the facts surrounding the rape. This uncertainty may lead to critical delays or a reluctance to report the rape and provide appropriate biological samples for use in apprehending the assailant.
Flunitrazepam abuse causes a number of adverse effects in the abuser, including drowsiness, dizziness, loss of motor control, lack of coordination, slurred speech, confusion, and gastrointestinal disturbances, lasting 12 or more hours. Higher doses produce respiratory depression. Chronic use of flunitrazepam can result in physical dependence and the appearance of withdrawal syndrome when the drug is discontinued. Flunitrazepam is known to impair cognitive and psychomotor functions affecting reaction time and therefore driving skills. The use of this drug in combination with alcohol is a particular concern as both substances appear to potentiate each other's toxicity.
To avoid being the victim of an flunitrazepam-induced assault, both men and women are commonly advised to never accept an open drink at a social event, particularly from a stranger. In addition, it is advisable for individuals to ask for beverages available in sealed containers and to insist upon opening the beverage themselves. Because flunitrazepam is colorless, ordorless and tasteless when dissolved in beverages it is very difficult to detect if a beverage has been spiked with the drug. Therefore, it is desirable to provide a simple, low cost and reliable method to avoid the insidious, disgusting and perilous dangers of suffering an unwanted flunitrazepam-related high or trip induced by a potential assailant slipping flunitrazepam into an unguarded beverage. Such a method would also be useful to law enforcement or medical personnel desiring a simple, rugged field test for the presence of flunitrazepam at crime scenes.
SUMMARY OF THE INVENTION
The present invention is an improvement on previous methods for the qualitative determination of flunitrazepam in a sample. In general, the method is initiated by obtaining a sample suspected to contain flunitrazepam. The sample may come from a beverage handed to a partygoer by a stranger. This beverage may contain ethanol in addition to flunitrazepam. If there is concern as to the safety of the beverage, an individual may use the present invention to detect whether or not the beverage was spiked with flunitrazepam.
According to the invention, flunitrazepam contained within the sample is simultaneously hydrolyzed and reduced to a hydrolyzed and reduced species by addition to the sample of a hydrolyzing agent and a reducing agent. The preferred reducing agent is tin (II) chloride. The preferred hydrolyzing agent is hydrochloric acid.
The reducing agent and hydrolyzing agent are provided in amounts to effectively reduce and hydrolyze flunitrazepam in the sample to the reduced and hydrolyzed species in an amount sufficient to provide a concentration of reduced and hydrolyzed species capable of being calorimetrically detected following Schiff base formation with a visualizing agent. Suitable visualizing compounds may be 4-dimethylaminocinnamaldehyde or 4-dimethylaminobenzaldehyde. The colorimetric indication is preferably visible to the naked eye of one practicing the invention as the invention is useful as a method practiced in the field by the general public, where no complex analytical steps are required or possible.
Other features and advantages of this invention will become clear to the reader after careful consideration is given to the following detailed description of the preferred exemplary embodiments thereof
DETAILED DESCRIPTION OF THE INVENTION
It was previously known in the field that certain benzodiazepines may be detected using a procedure requiring the hydrolysis of those benzodiazepines to the corresponding 2-aminobenzophenones. See Laudszun and Kovar (Pharm. Acta Helv. 66, 268 (1991)). Scheme 1 below illustrates the previously-known reaction with a general benzodiazepine (1) being hydrolyzed to a 2-aminobenzophenone (2) in the presence of hydrochloric acid and heat.
Scheme 1 further illustrates the resulting 2-aminobenzophenone (2) being subsequently reacted with a conjugated aldehyde to yield a highly conjugated colored species (3). Specifically, the highly conjugated colored species (3) is formed via Schiff base formation between the 2-aminobenzophenone (2) and conjugated aldehyde 4-dimethylaminocinnamaldehyde.
However, Scheme 1 shown above is understood to have certain limitations. Scheme 2 below illustrates that the detection method of Scheme 1 is incapable of detecting particular species of benzodiazepines, most notably flunitrazepam.
The reason for the ineffectiveness of the above-described test for flunitrazepam is believed due to the presence of a nitro group at position 5 of the aminobenzophenone (5) resulting from hydrolysis of flunitrazepam (4). The nitro group is believed to reduce the nucleophilicity of the amino group located para to the nitro group due to the nitro group's strong electron drawing effects. Therefore, it is widely held that the hydrolyzed form (5) of flunitrazepam cannot form corresponding color compounds by the reactions shown in Scheme 1. Based upon the preceding rationale, the procedure shown in Scheme 1 is most likely ineffective in detecting all benzodiazepine species having electron withdrawing groups located at the para and presumably ortho positions relative to the respective amino group.
The present invention provides an improvement over the previous method of Scheme 1 by reducing or eliminating the electron withdrawing effects of the nitro group at the 7-position of flunitrazepam (4) thereby providing a benzophenone product (6) capable of undergoing Schiff base formation with a visualizing compound such as 4-dimethylaminocinnamaldehyde to form a colored species (7). According to the invention, the nitro group is reduced to a hydroxylamino or amino functionality simultaneously with hydrolysis of the flunitrazepam and prior to addition of the visualizing compound. Scheme 3 below illustrates an exemplary chemical reaction according to the invention wherein f
Cole Monique T.
Godfrey & Kahn S.C.
R. E. Davis Chemical Corporation
Warden Jill
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