Drug info - Erimin - Nimetazepam ("Happy-5's")

[Kipperflap]

or sometimes called Happy 5

Has anyone heard of this before?

Thanks in advance

[Expat98]

The correct spelling is "erimin", and the chemical name is nimetazepam. It's a benzodiazepine, so this thread should be moved to that forum (and the title should be corrected so the search engine can find it).

Erimin originated in Japan, and it's very popular for recreational use in Malaysia, Singapore, and Indonesia.

It is chemically related to nitrazepam (its desmethyl derivative), but has a faster onset and shorter half-life, making it preferred for recreational use. From what I hear, nitrazepam is a favorite among experienced benzo users, so if erimin/nimetazepam is even better then it must be pretty good. SWIM has never tried either one...

[Expat98]

Here's some info from erimin.com (I haven't bothered to correct all the spelling and grammar mistakes.)



Erimin/Nimetazepam is a benzodiazepine originated from Japan. It is said to be invented after the chemical nitrazepam was invented in the western countries. It has a faster onset and a shorter half-life compared to Nitrazepam making it a drug of abuse. Nimetazepam distributed more rapidly in the brain than its desmethyl derivative (nitrazepam)[faster onset]. The brain concentration of the active metabolites of the former was about twice that of Nitrazepam at 1hour after oral administration.

At least four kinds of reactions were involved in the biotransformation of nimetazepam and its desmethyl derivative (nitrazepam) (demethylation at N-1,hydroxylation at C-3, reduction of the nitro group at C-7 to the amino group and (iv) subsequent acetylation of the amino group. The 1-N-demethylation of nimetazepam was slow compared with the other three reactions. Nimetazepam was rapidly hydroxylated at C-3, while the 3-hydroxylation of its desmethyl derivative (nitrazepam) was very slow.

The reduction of the nitro group at C-7 and subsequent acetylation were important routes for the excretion of these drugs. To simplify things Erimin 5 (nimetazepam) is a recreational chemical.


About Erimin in Singapore



It first appeared on the local drug scene three years ago when more than 90,000 pills were seized. Now, the tranquilliser Erimin-5, or nimetazepam, has become the drug of choice among abusers. Many of the 793 drug abusers arrested last year were on Erimin-5, according to the CNB’s annual drugs report. Erimin-5 had displaced the previous year's favoured drug, ketamine.

Testing for Erimin-5 was began in January 2004. There are people who still think Erimin-5 is not detectable. The truth is Nimetazepam is classified under the Benzodiazepine family and when an accuse is tested positive from the Instant urine test for benzodiazepines , the urine sample will be taken to the Health Science Authority for the analysis for the chemical .

In the streets an Erimin-5 tablet costs between S$6 (RM13.80) and S$8 (RM18.40), while 1g of ketamine costs between S$40 (RM92) and S$50 (RM115).

Unlike so-called “party drugs” like Ecstasy and ketamine, Erimin-5 is a depressant and seen as a “soft” drug. It can also be obtained easily compaired to other drugs

In Singapore Erimin is Scheduled under the Misuse of drug act ( Chapter 185 ) It is scheduled under class C which carries a Mandory Jaill therm. A trafficker can face up to a maximum of 10 years in prison and 5 Strokes of the cane.



As for illegal possession or consumption of Nimetazepam a person can face up to 10 years of imprisonment or S$20,000 fine or both.

[Expat98]

Here's some more technical info from an article on the US DEA website (but written by Malaysian researchers). Original article at http://www.usdoj.gov/dea/programs/fo...04/page27.html

The Quantitation of Nimetazepam in Erimin-5 Tablets
and Powders by Reverse-Phase HPLC

Yong Kiong Chong, Muzaiyanah Mohd Kaprawi, and Kee Bian Chan*

Narcotics Section, Forensic Division
Department of Chemistry Malaysia
Jalan Sultan, 46661 Petaling Jaya
Malaysia
[email: kbchan -at- kimia.gov.my]

ABSTRACT: The sedative-hypnotic nimetazepam in “Erimin 5” tablets and powders was quantitated by reverse phase HPLC. The selectivity, precision, and accuracy of the procedure are presented.

KEYWORDS: Nimetazepam, Erimin-5, Benzodiazepines, HPLC, Forensic Chemistry

Figure 1: Structure of Nimetazepam

Introduction

Since its appearance in illicit drug markets in Malaysia in the mid-1980’s, the benzodiazepine nimetazepam (Figure 1) has become the most commonly abused sedative in the country (midazolam and triazolam are the (distant) second and third most abused sedatives). The popularity of nimetazepam is due in part to its wide availability and relatively low price on the local black markets, and in part due to its long activity. Most of the abusers are believed to be heroin addicts, who use it as a substitute for heroin when its availability is low. More recently, however, nimetazepam has also been used as a sedative by methamphetamine abusers to help them sleep after binging (in fact, the rise in nimetazepam abuse roughly parallels the rise in methamphetamine abuse in Malaysia). The illicit use of nimetazepam is continuing to increase, as shown by the number and size of seizures made over the past few years. For example, a seizure of 310,000 tablets was made in June 2002 at a residence near the capital city (Kuala Lumpur). Tablet submissions to the Central Laboratory have been in the hundreds of thousands for each of the three years 2002 - 2004. Similar abuse of nimetazepam has been reported in neighboring countries.

The two primary forms of nimetazepam encountered in Malaysia are a commercial product (Erimin-5 tablets in blister packs (see Photos 1 - 2)) or Erimin-5 counterfeits, and an orange colored powder that appears to be either finely crushed tablets or the tablet mixture prior to tableting. Commercially prepared tablets nominally weigh about 170 mg and contain about 5 mg of nimetazepam each. However, as noted above, many of the Erimin-5 tablets submitted to the Narcotics Section appear to actually be counterfeit products that contain nimetazepam and/or various other benzodiazepines, notably diazepam and nitrazepam, in varying quantities.

Nimetazepam was added to the Malaysian Dangerous Drugs Act 1952 in May, 2001 and is currently the only benzodiazepine controlled in Malaysia. The analysis of nimetazepam by a variety of techniques has been previously reported (1-4), including by CE and CEC (5-7), Color Testing (8), FTIR (9), GC (10-12), HPLC and HPLC/MS (13-18), TLC (17,19), and UV/Vis (20). Herein, we report the quantitation of nimetazepam in seized tablets and powders with reverse-phase HPLC, using an external standard method.

Photo 1 - Front and Back Views of a Erimin-5 Blister
Pack (Note: This is a Suspected Counterfeit)

Photo 2 - Closeup of an Erimin-5 Tablet (Front and Reverse)

Experimental

Chemicals
HPLC grade methanol and chloroform were purchased from Merck, while AR grade orthophosphoric acid (84 %) was purchased from Ajax (Australia). Nimetazepam (free-base) standard of 100 % purity was kindly provided free of charge by Sumitomo Chemical Company (Tokyo, Japan). The following benzodiazepines (as free bases) were obtained from the United Nations Drug Control Programme (UNDCP) in Vienna (Austria): Nitrazepam, bromazepam, tetrazepam, flunitrazepam, oxazepam, lorazepam, clorazepate dipotassium (salt), diazepam, flurazepam, and medazepam. Unfortunately, midazolam and triazolam standards were unavailable, and so were not run.

Instrumentation
A Hewlett Packard Series 1050 HPLC was used with the following parameters:
Column C-18, 5 µm particle size, 15 cm x 4.6 mm i.d. (from Alltech). Detector: UV at 265 nm. Mobile phase: Methanol:Water (50:65). The pH was adjusted to 4.0 with orthophosphoric acid (to a mixture of 500 mL of methanol and 650 mL of water was added one drop of orthophosphoric acid) (21). Column temperature: 25° C (ambient temperature). Flow rate: 1.5 mL/minutes. Average Pressure: 155 bar. Injection: 20 µL by Rheodyne loop injector. Attenuation: 4 (Integrator).

Standard Solutions for Linearity Study and Calibration
Standard solutions containing 0.020, 0.040, 0.080, 0.120, 0.160, 0.200 and 0.240 mg/mL of nimetazepam were prepared in a mixture of methanol/chloroform (5:1) (note that the chloroform was added to better solubulize the tablet materials, and had no adverse effects on the chromatography).

Quantitative Analysis of Samples
About 70 - 100 mg of homogenized tablet material was accurately weighed into a 25 mL volumetric flask and made up to volume with a mixture of methanol/chloroform (5:1). The sample solution was ultrasonicated for 5 minutes and filtered through a 0.45 µm filter before injected onto the column. Quantitation was by external standard and with reference to the peak area of the 0.120 mg/mL nimetazepam standard.

Procedure for Standard Addition Method
(i) 350.80 mg of tablet material was weighed into a 100 mL volumetric flask, made up to volume with methanol/chloroform (5:1), and ultrasonicated for 5 minutes. (ii) 10 mL of the solution in (i) (i.e., equivalent to 35.08 mg of tablet material) was pipetted into each of five 25 mL volumetric flasks. (iii) The following aliquots of nimetazepam standard stock solution (1.00 mg/mL) were pipetted into the solutions in (ii): 0, 1, 2, 3, and 4 mL. (iv) The solutions were made up to volume (i.e., 25 mL) with methanol/chloroform (5:1). (v) The solutions were filtered through a 0.45 µm filter and injected into the HPLC. (vi) A graph of area versus concentration of nimetazepam (mg/mL) was plotted using Excel and the native nimetazepam content calculated.

Results and Discussion

Selectivity
Identification of benzodiazepines is accomplished in this laboratory by GC/MS. However, GC and GC/MS are problematic for quantitation of nimetazepam and some related benzodiazepines due to thermal degradation at injector port temperatures, and so HPLC was selected for quantitation. Because of the wide diversity of chemical structures and solubility characteristics among the benzodiazepines, no single HPLC method will separate all of them. The specificity of the method presented herein was defined in terms of the benzodiazepines typically found in Malaysia. The identities and retention times of these benzodiazepines using the presented methodology are presented in Table 1.

Table 1: Retention Times of Benzodiazepines (HPLC)

Benzodiazepine / Retention Time (min)
Nitrazepam 6.91Bromazepam 7.62
Tetrazepam 7.80
Flunitrazepam 8.54
Oxazepam 8.55
Lorazepam 8.93Nimetazepam 9.94
Clorazepate dipotassium 17.07
Diazepam 26.63
Flurazepam NE
Medazepam NE


Figure 2: HPLC of Nitrazepam and Nimetazepam Note: Slight variations in Retention Times between Table 1 and Figure 2 are due to natural variations over time; the order of elution was found to be consistent from run to run.

Of the selected benzodiazepines, flunitrazepam, oxazepam, and lorazepam elute closest to nimetazepam, and give partially overlapping peaks. Thus, the presented HPLC method is not appropriate for samples containing these compounds. Fortunately, however, experience has shown that these three benzodiazepines are very rarely present in tablets or powders containing nimetazepam. A few samples of “Erimin-5” tablets have been found to contain diazepam instead of nimetazepam; however, diazepam elutes much later than nimetazepam. A typical HPLC chromatogram of a mixture of nitrazepam and nimetazepam is displayed in Figure 2.

Calibration Curve and Linearity
The calibration graph (Figure 3) for the analysis was found to be linear from 0.020 mg/mL to 0.240 mg/mL. From linear regression analysis, the correlation coefficient was better than 0.99, and the percent difference between the known concentration and the predicted concentration from the regression equation was less than 5 %. In routine analyses a single point calibration was used.

Precision
The precision of the method was assessed by 10 replicate analyses of a homogenized sample of “Erimin 5” tablets. Injections were all made in triplicate and quantitation was against the 0.120 mg/mL standard. The mean content of nimetazepam was found to be 3.1 % with a relative standard deviation of 4.4 %.

Figure 3: Calibration Curve of Nimetazepam

Accuracy
The accuracy of the method was assessed by analyzing two laboratory prepared mixtures, and re-analysis of the sample which was used for the precision study by the method of standard addition.

Analysis of Laboratory Prepared Mixtures
Owing to the limited supply of pure nimetazepam reference standards, only two synthetic mixtures were prepared, simulating 5 mg/tablet and 3 mg/tablet. Both the samples were prepared in lactose and contained 3.5 % and 1.7 % of nimetazepam, respectively. Replicate analyses (n = 7) of these two mixtures were made and the results assessed using the Student t-statistic:

For both samples it was found that the t value did not exceed the critical value derived by statistical analysis, showing that there was no proven evidence of difference between the experimental value and the theoretical value at 95 % confidence level.

Standard Addition Method
The same nimetazepam tablet material which was used in the precision study was re-analyzed using the standard addition method. From the standard addition calibration graph (Figure 4) the amount of nimetazepam was found to be 3.1 %. This agreement with the precision study mean value shows that there is no interference from the tablet excipient materials, and thus to some extent shows that the method is accurate.

Figure 4: Standard Addition Calibration Curve

Acknowledgments

The authors would like to thank Dr. Yoji Sakito, Manager, Corporate Planning & Coordination Office, Sumitomo Chemical Company Ltd, Tokyo, Japan for the nimetazepam reference standard used in this study.

References

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3. Nimetazepam. http://chrom.tutms.tut.ac.jp/JINNO/D...metazepam.html
   
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15. Catabay A, Taniguchi M, Jinno K, Pesek JJ, Williamsen E. Separation of 1,4-benzodiazepines and analogs using cholesteryl-10-undecenoate bonded phase in microcolumn liquid chromatography. J. Chromatogr. Sci. 1998;36(3):111-118.
    
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[Micklemouse]

Title changed & topic moved. Cheers Expat!

[Psych0naut]

Nimetazepam is the only prescription benzodiazepine in most Asian countries, and deemed obsolete by the medical world in Western countries. That must mean it's pretty recreational, probably in the area of Rohypnol(flunitrazepam), it's a damn shame they are almost impossible to get in the West.

[Expat98]

Originally Posted by Psych0naut

Nimetazepam is the only prescription benzodiazepine in most Asian countries

I can only really speak for Southeast Asia, but I can tell you for sure that other benzos (e.g., Valium and Xanax) are readily available in several SE Asia countries, both from legitimate sources (e.g., through a reputable hospital with a prescription) and non-legitimate sources (e.g., over the counter with no prescription necessary).

Although I can't speak from personal experience, I'd be very surprised if benzos other than nimetazepam weren't available by prescription in other Asian countries (e.g., Japan, South Korea, Taiwan).

[Kipperflap]

Thanks guys!
Friends have recently been taking this drug in clubs in London and I was curious as to what it is like.
I found information (like above) saying it was a depressant but friends were telling me it had very similar effects to ecstasty. I was dubious.

[Psych0naut]

If SWIY has acces to nimetazepam, than certainly go for it! They're very, very rare here in Western-Europe, so the change of finding them again is slim.

[wearestardust]

Nimetazepam is the benzo SWIM would most like to get his hands on since reading that it produced more euphoria than any other benzo. And he feels euphoric on alprazolam and temazepam...
WAS