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Beholder
Regular

Russia,
2017-11-30 15:14

Posting: # 18027
Views: 2,700
 

 LLOQ: higher or lower? [Bioanalytics]

Hi to everybody!

May be it is a strange question, but nevertheless: using which LLOQ the chances to establish BE are higher: higher (5 ng/ml) or lower (0.5 ng/ml)?

Thx in advance

Best regards
Beholder
cakhatri
Regular

India,
2017-12-04 09:52

@ Beholder
Posting: # 18033
Views: 2,317
 

 LLOQ: higher or lower?

Hi,

Any LLOQ you select, should be based on justification. In general it is 1/32 of the reported Cmax (Cmax*1/32). This is assumed based on the standard calculation of 5 half lives and usually will be sufficient.

Regarding which Cmax to select - You should consider the reported Cmax or if range is available, consider the lower range (if 80-100 ng/mL Cmax, consider 80 and calculate 1/32)

You also should look at the sampling time points in protocol. if that is beyond 5 half lives, the LLOQ should be lowered accordingly

If you are conducting a study with truncated design, the LLOQ need not be 1/32 but higher (1/16 or 1/8) because usually for truncated design the sampling is restricted to 1 or 2 half life and hence LLOQ can be taken higher.

With proper selection of LOQ, you will be able to minimize the BLQ (Below limit of Quantification) values and proper estimation of AUC0-t and AUC0-inf.

Regards
Chirag
BE-proff
Senior

Russia,
2017-12-07 09:25

@ cakhatri
Posting: # 18040
Views: 2,164
 

 LLOQ: higher or lower?

Hi Chirag,

Where did you take ratio 1/32?
From a guide or from your experience?

Prof
mittyri
Senior

Russia,
2017-12-07 15:57

@ BE-proff
Posting: # 18042
Views: 2,151
 

 32=2^5 half lives

Dear BE-proff,

I suppose
2^5 = 32
1/2^5 = 1/32

So Chirag is referring to 5-half lives rule (I do not discuss its applicability here)

Kind regards,
Mittyri
cakhatri
Regular

India,
2017-12-11 07:39

@ mittyri
Posting: # 18054
Views: 2,093
 

 32=2^5 half lives

Hi,
That's correct. 1/32 is equivalent to 5 half life
Regards
Chirag
xtianbadillo
Junior

Mexico,
2018-01-18 15:51

@ cakhatri
Posting: # 18215
Views: 1,744
 

 LLOQ: higher or lower?

As Cakhatri said a proper LLOQ let you a proper estimation of AUC0-t and AUC0-inf and to avoid BLQ. "for bioequivalence studies the LLOQ should be not higher than 5% of the Cmax, while such a low LLOQ may be not necessary for exploratory pharmacokinetic studies EMA" for BE at least 80% of AUC0-inf is required, so a low LLOQ is recommended.

In my experience I go for -2SD of the Cmax and the result result is divided by 20:
For instance Cmax 1000 +/-100, so 800/20 = LLOQ = 40; in this example, according to EMA should be not higher than 50, so 40 is OK

Doing this I have reduced my BLO;

1000/32 = 31.25 is better than 40 :-)
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