The identification of (-)-trans-tadalafil, tadalafil, and sildenafil in counterfeit Cialis and the optical purity of tadalafil stereoisomers.
Four blisters with suspect Cialis (tadalafil) 20mg tablets were screened for authenticity using near infrared spectroscopy (NIRS) and for the presence of phosphodiesterase 5 (PDE-5) inhibitors using LC-DAD-MS. All samples were identified as counterfeit Cialis and contained sildenafil or a combination of tadalafil and sildenafil. Although the tablets contained efficacious amounts of PDE-5 inhibitors, neither the active ingredient nor the dosage corresponded to the description on the blister. This is the first reported case of a diastereomeric mixture of tadalafil and trans-tadalafil (3:1) being identified in a counterfeit medicine. The LC-DAD-CD revealed that both diastereomers had a high optical purity. The optical rotation of the diastereomeric mixture was measured indicating the presence of (-)-trans-tadalafil, which is the only other stereoisomer with some PDE-5 inhibitory activity. As no safety profiles are known for the stereoisomers of tadalafil, there is a potential health risk. In addition, the optical purity of tadalafil needs to be taken into account when calculating the dosage in illegal medicines.
National Institute for Public Health and the Environment, Postbox 1, 3721MA Bilthoven, The Netherlands. venhuisb@rivm.nl
B J
BJ
Venhuis
G
G
Zomer
M J
MJ
Vredenbregt
D
D
de Kaste
D002243:Carbolines / Q000032:analysis* / Q000737:chemistry*; D004340:Drug Contamination; D005607:Fraud; D009904:Optical Rotation; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry*; D011687:Purines / Q000032:analysis / Q000737:chemistry; D000068677:Sildenafil Citrate; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013237:Stereoisomerism; D013450:Sulfones / Q000032:analysis* / Q000737:chemistry*; D000068581:Tadalafil
D002243:Carbolines; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068581:Tadalafil; D000068677:Sildenafil Citrate